HLA-B Antigens: Class I human histocompatibility (HLA) surface antigens encoded by more than 30 detectable alleles on locus B of the HLA complex, the most polymorphic of all the HLA specificities. Several of these antigens (e.g., HLA-B27, -B7, -B8) are strongly associated with predisposition to rheumatoid and other autoimmune disorders. Like other class I HLA determinants, they are involved in the cellular immune reactivity of cytolytic T lymphocytes.HLA Antigens: Antigens determined by leukocyte loci found on chromosome 6, the major histocompatibility loci in humans. They are polypeptides or glycoproteins found on most nucleated cells and platelets, determine tissue types for transplantation, and are associated with certain diseases.HLA-B27 Antigen: A specific HLA-B surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the HLA-B*27 allele family.HLA-A Antigens: Polymorphic class I human histocompatibility (HLA) surface antigens present on almost all nucleated cells. At least 20 antigens have been identified which are encoded by the A locus of multiple alleles on chromosome 6. They serve as targets for T-cell cytolytic responses and are involved with acceptance or rejection of tissue/organ grafts.HLA-B7 Antigen: A specific HLA-B surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the HLA-B*07 allele family.Antigens: Substances that are recognized by the immune system and induce an immune reaction.HLA-B35 Antigen: A specific HLA-B surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the HLA-B*35 allele family.HLA-B51 Antigen: A specific HLA-B surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the HLA-B*51 allele family.HLA-B15 Antigen: A specific HLA-B surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the HLA-B*15 allele family.HLA-B8 Antigen: A specific HLA-B surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the HLA-B*08 allele family.Antigens, Bacterial: Substances elaborated by bacteria that have antigenic activity.HLA-B52 Antigen: A specific HLA-B surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the HLA-B*52 allele family.Antigens, Neoplasm: Proteins, glycoprotein, or lipoprotein moieties on surfaces of tumor cells that are usually identified by monoclonal antibodies. Many of these are of either embryonic or viral origin.HLA-B44 Antigen: A specific HLA-B surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the HLA-B*44 allele family.Antigens, Surface: Antigens on surfaces of cells, including infectious or foreign cells or viruses. They are usually protein-containing groups on cell membranes or walls and may be isolated.HLA-B38 Antigen: A specific HLA-B surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the HLA-B*38 allele family.Antigens, Viral: Substances elaborated by viruses that have antigenic activity.HLA-B40 Antigen: A specific HLA-B surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the HLA-B*40 allele family.HLA-B14 Antigen: A specific HLA-B surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the HLA-B*14 allele family.HLA-B18 Antigen: A specific HLA-B surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the HLA-B*18 allele family.Antigens, Protozoan: Any part or derivative of any protozoan that elicits immunity; malaria (Plasmodium) and trypanosome antigens are presently the most frequently encountered.Antigens, Polyomavirus Transforming: Polyomavirus antigens which cause infection and cellular transformation. The large T antigen is necessary for the initiation of viral DNA synthesis, repression of transcription of the early region and is responsible in conjunction with the middle T antigen for the transformation of primary cells. Small T antigen is necessary for the completion of the productive infection cycle.Spondylitis, Ankylosing: A chronic inflammatory condition affecting the axial joints, such as the SACROILIAC JOINT and other intervertebral or costovertebral joints. It occurs predominantly in young males and is characterized by pain and stiffness of joints (ANKYLOSIS) with inflammation at tendon insertions.HLA-B39 Antigen: A specific HLA-B surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the HLA-B*39 allele family.Antigens, Fungal: Substances of fungal origin that have antigenic activity.Antigens, CD: Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.H-2 Antigens: The major group of transplantation antigens in the mouse.Antigens, Helminth: Any part or derivative of a helminth that elicits an immune reaction. The most commonly seen helminth antigens are those of the schistosomes.HLA-DR Antigens: A subclass of HLA-D antigens that consist of alpha and beta chains. The inheritance of HLA-DR antigens differs from that of the HLA-DQ ANTIGENS and HLA-DP ANTIGENS.Epitopes: Sites on an antigen that interact with specific antibodies.Histocompatibility Antigens: A group of antigens that includes both the major and minor histocompatibility antigens. The former are genetically determined by the major histocompatibility complex. They determine tissue type for transplantation and cause allograft rejections. The latter are systems of allelic alloantigens that can cause weak transplant rejection.Carcinoembryonic Antigen: A glycoprotein that is secreted into the luminal surface of the epithelia in the gastrointestinal tract. It is found in the feces and pancreaticobiliary secretions and is used to monitor the response to colon cancer treatment.Antigens, Viral, Tumor: Those proteins recognized by antibodies from serum of animals bearing tumors induced by viruses; these proteins are presumably coded for by the nucleic acids of the same viruses that caused the neoplastic transformation.Receptors, Antigen, T-Cell: Molecules on the surface of T-lymphocytes that recognize and combine with antigens. The receptors are non-covalently associated with a complex of several polypeptides collectively called CD3 antigens (ANTIGENS, CD3). Recognition of foreign antigen and the major histocompatibility complex is accomplished by a single heterodimeric antigen-receptor structure, composed of either alpha-beta (RECEPTORS, ANTIGEN, T-CELL, ALPHA-BETA) or gamma-delta (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA) chains.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Arthritis, Reactive: An aseptic, inflammatory arthritis developing secondary to a primary extra-articular infection, most typically of the GASTROINTESTINAL TRACT or UROGENITAL SYSTEM. The initiating trigger pathogens are usually SHIGELLA; SALMONELLA; YERSINIA; CAMPYLOBACTER; or CHLAMYDIA TRACHOMATIS. Reactive arthritis is strongly associated with HLA-B27 ANTIGEN.Histocompatibility Antigens Class I: Membrane glycoproteins consisting of an alpha subunit and a BETA 2-MICROGLOBULIN beta subunit. In humans, highly polymorphic genes on CHROMOSOME 6 encode the alpha subunits of class I antigens and play an important role in determining the serological specificity of the surface antigen. Class I antigens are found on most nucleated cells and are generally detected by their reactivity with alloantisera. These antigens are recognized during GRAFT REJECTION and restrict cell-mediated lysis of virus-infected cells.HLA-A2 Antigen: A specific HLA-A surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the HLA-A*02 allele family.Histocompatibility Antigens Class II: Large, transmembrane, non-covalently linked glycoproteins (alpha and beta). Both chains can be polymorphic although there is more structural variation in the beta chains. The class II antigens in humans are called HLA-D ANTIGENS and are coded by a gene on chromosome 6. In mice, two genes named IA and IE on chromosome 17 code for the H-2 antigens. The antigens are found on B-lymphocytes, macrophages, epidermal cells, and sperm and are thought to mediate the competence of and cellular cooperation in the immune response. The term IA antigens used to refer only to the proteins encoded by the IA genes in the mouse, but is now used as a generic term for any class II histocompatibility antigen.HLA-B37 Antigen: A specific HLA-B surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the HLA-B*37 allele family.Proliferating Cell Nuclear Antigen: Nuclear antigen with a role in DNA synthesis, DNA repair, and cell cycle progression. PCNA is required for the coordinated synthesis of both leading and lagging strands at the replication fork during DNA replication. PCNA expression correlates with the proliferation activity of several malignant and non-malignant cell types.Spondylarthritis: Inflammation of the joints of the SPINE, the intervertebral articulations.Cross Reactions: Serological reactions in which an antiserum against one antigen reacts with a non-identical but closely related antigen.Prostate-Specific Antigen: A glycoprotein that is a kallikrein-like serine proteinase and an esterase, produced by epithelial cells of both normal and malignant prostate tissue. It is an important marker for the diagnosis of prostate cancer.O Antigens: The lipopolysaccharide-protein somatic antigens, usually from gram-negative bacteria, important in the serological classification of enteric bacilli. The O-specific chains determine the specificity of the O antigens of a given serotype. O antigens are the immunodominant part of the lipopolysaccharide molecule in the intact bacterial cell. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)Receptors, Antigen, B-Cell: IMMUNOGLOBULINS on the surface of B-LYMPHOCYTES. Their MESSENGER RNA contains an EXON with a membrane spanning sequence, producing immunoglobulins in the form of type I transmembrane proteins as opposed to secreted immunoglobulins (ANTIBODIES) which do not contain the membrane spanning segment.T-Lymphocytes: Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.

*  RCSB PDB - 1ZHK: Crystal structure of HLA-B*3501 presenting 13-mer EBV antigen LPEPLPQGQLTAY Structure Summary Page

B-35 alpha chain A 276 Homo sapiens Fragment: Extracellular domains alpha 1 Gene Name(s): HLA-B Gene View HLAB ... Crystal structure of HLA-B*3501 presenting 13-mer EBV antigen LPEPLPQGQLTAY. *DOI: 10.2210/pdb1zhk/pdb ... B 99 Homo sapiens Gene Name(s): B2M Gene View CDABP0092 HDCMA22P ...
rcsb.org/pdb/explore.do?structureId=1ZHK

*  PDB 1jws structure summary ‹ Protein Data Bank in Europe (PDBe) ‹ EMBL-EBI

HLA class II histocompatibility antigen, DRB1-1 beta chain Chain: B Molecule details › Chain: B. Length: 190 amino acids. ... MHC antigen-recognition domain * Occurring in:. *HLA class II histocompatibility antigen, DR alpha chain. *HLA class II ... HLA class II histocompatibility antigen, DR alpha chain. *HLA class II histocompatibility antigen, DRB1-1 beta chain. '> ... HLA class II histocompatibility antigen, DR alpha chain. *HLA class II histocompatibility antigen, DRB1-1 beta chain. '> ...
ebi.ac.uk/pdbe/entry/pdb/1jws

*  Induction of B cell apoptosis by TH0, but not TH2, CD4+ T cells.

Ligation of MHC molecules on the surface of B cells, however, has not only been implicated in antigen ... Engagement of the T cell receptor molecules with MHC-antigen complexes presented by B cells ascertains antigen specificity in T ... 0/Antigens, CD; 0/Antigens, CD3; 0/Cytokines; 0/HLA-DR Antigens; 0/Interferon-gamma, Recombinant; 0/Interleukin-2; 0/Receptors ... Antigens, CD / immunology, physiology. Antigens, CD3 / immunology, physiology. Apoptosis / drug effects, immunology*. B- ...
biomedsearch.com/nih/Induction-B-cell-apoptosis-by/7860739.html

*  Evaluating the Safety and Effectiveness of an Umbilical Cord Blood Stem Cell Transplant (BMT CTN 0604) - Full Text View -...

... at the antigen level) or DRB1 (at the allele level) loci. Each unit must be a 4 to 6 HLA-A, B, and DRB1 antigen matched to each ... Have an HLA-matched, related, or 7 or 8/8 HLA allele matched (HLA-A, -B, -Cw, -DRB1) related donor able to donate ... Each unit must match at a minimum of 4 of 6 at HLA-A, -B, -DRB1 loci with the recipient. This may include 0 to 2 antigen ... Lymphoma, B-Cell. Lymphoma, Large B-Cell, Diffuse. Lymphoma, Follicular. Precursor B-Cell Lymphoblastic Leukemia-Lymphoma. ...
https://clinicaltrials.gov/ct2/show/NCT00864227

*  Vorinostat, Tacrolimus, and Methotrexate in Preventing GVHD After Stem Cell Transplant in Patients With Hematological...

The donor and recipient must have a human leukocyte antigen (HLA)-8/8 allelic match at the HLA-A, -B, -C, and -DRB1; high- ... Lymphoma, B-Cell. Lymphoma, Mantle-Cell. Leukemia, Myelogenous, Chronic, BCR-ABL Positive. Lymphoma, B-Cell, Marginal Zone. ... B-cell Lymphoma Diffuse Large B-Cell Lymphoma Lymphosarcoma Mantle Cell Lymphoma Burkitt Lymphoma Chronic Myelomonocytic ... Cutaneous B-cell Non-Hodgkin Lymphoma Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue Graft ...
https://clinicaltrials.gov/ct2/show/NCT01789255?recr=Open&cond="Hodgkin Disease"&rank=12

*  Plus it

The C1R cell line is a human plasma leukemia cell line that does not express endogenous HLA-A or HLA-B antigens (34). C1R-A2 ... HLA-A3, and HLA-A24 have recently been reported. CD8+ T-cell responses to these HLA-A2, HLA-A3, and HLA-A24 epitopes were ... 7A and B). The AsPC-1 cell line, a HLA-A2-negative cell line not lysed by T-1991-P547, was used as a negative control (Fig. 7C ... Mesothelin-derived HLA-A2-, HLA-A3-, and HLA-A24-restricted CTL 9-mer epitopes have been previously reported (24). These ...
clincancerres.aacrjournals.org/content/11/17/6342

*  Safety and Efficacy of Pentostatin and Low Dose TBI With Allogenic Peripheral Blood Stem Cell Transplant

HLA genotypically matched relative. - siblings or first-degree relatives matched at HLA-A, B, or DR loci (6 antigen match). are ... HLA matched unrelated volunteer donor. - unrelated donor matched at HLA-A, B, or DR loci (6 antigen match) are acceptable. ... One antigen mismatch related or unrelated donor will also be acceptable, molecular. typing needs to be used at each H LA-A, B, ... Small Lympho(plasma)cytic Lymphoma (B-SLL, B-LPL): recurrence after a front line regimen. (related donor transplant), or ...
knowcancer.com/cancer-trials/NCT00571662/

*  Single or Double Umbilical Cord Blood Unit Transplantation Followed by GVHD Prophylaxis With FK506 and MMF

No available HLA identical or 1 antigen/allele mismatched (Class I-A, B or Class II. DR locus) related donor. - No available ... Umbilical Cord Blood Unit-HLA Typing. - At least a HLA 4/6 match (Class I-A,B by low resolution, Class II-DR by high. ... For recipients of HLA-matched or HLA-1 antigen mismatched UCB grafts, the actuarial. probability of hematopoietic recovery at ... Acute GVHD has occurred very infrequently in recipients of HLA-matched and HLA-1 antigen. mismatched UCB SCT. The actuarial ...
knowcancer.com/cancer-trials/NCT00244036/

*  HLA-DPB1 Gene - GeneCards | DPB1 Protein | DPB1 Antibody

Complete information for HLA-DPB1 gene (Protein Coding), Major Histocompatibility Complex, Class II, DP Beta 1, including: ... Class II molecules are expressed in antigen presenting cells (APC: B lymphocytes, dendritic cells, macrophages). The beta chain ... HLA-DPA1 HLA-DPB1 HLA-DQB1 HLA-DQA2 HLA-DOB HLA-DRB1 HLA-DOA PRRT1 HLA-DQB2 SYNGAP1 ... HLA-DPB1 HLA-DPB2 HLA-DPA1 RPL32P1 RING1 RXRB HLA-DMA HLA-DPA3 RPS18 GC06P033079 ...
genecards.org/cgi-bin/carddisp.pl?gene=HLA-DPB1&rf=/home/genecards/current/website/carddisp.pl&milli_pathways=6

*  Hepatitis B Vaccine Genetics: A Substudy of ATN 024 and ATN 025 - Full Text View - ClinicalTrials.gov

... immune responses to hepatitis B vaccine in individuals and confirm the correlation of specific human leukocyte antigen (HLA) ... Hepatitis B vaccines. HIV-infected adolescents. Hepatitis B infection (negative). HIV vaccine trial. ... To confirm the correlation of HLA-DRB1 and HLA-DQB1 alleles and haplotypes with HBV antibody concentrations and antibody decay ... Hepatitis B Vaccine Genetics: A Substudy of ATN 024 and ATN 025. This study has been completed. ...
https://clinicaltrials.gov/show/NCT00142740?order=620

HLA B7-DR15-DQ6HLA-B38: HLA-B38 (B38) is an HLA-B serotype. The serotype identifies the B*38 allele products of the HLA-B gene-locus.HLA-A: HLA-A is a group of human leukocyte antigens (HLA) that are coded for by the HLA-A locus, which is located at human chromosome 6p21.3.History and naming of human leukocyte antigens: Human leukocyte antigens (HLA) began as a list of antigens identified as a result of transplant rejection. The antigens were initially identified by categorizing and performing massive statistical analyses on interactions between blood types.Cancer/testis antigen family 45, member a5SpondylitisCD36 antigen: CD36 antigen is a transmembrane, highly glycosylated, glycoprotein expressed by monocytes, macrophages, platelets, microvascular endothelial cells and adipose tissues. CD36 recognises oxidized low density lipoprotein, long chain fatty acids, anionic phospholipids, collagen types I, IV and V, thrombospondin and Plasmodium falciparum infected erythrocytes.Cryptic self epitopes: In immunology, cryptic self epitopes are a source of autoimmunity.Carcinoembryonic antigen: Carcinoembryonic antigen (CEA) describes a set of highly related glycoproteins involved in cell adhesion. CEA is normally produced in gastrointestinal tissue during fetal development, but the production stops before birth.Kinetic-segregation model of T cell activationMonoclonal antibody therapyReactive arthritisAntigen presentation: Antigen presentation describes a vital process of the immune system. Immune cells cannot "see inside" other cells, which may be infected with viruses or bacteria, and thus rely on information conveyed by fragments of intracellular components being presented on major histocompatibility complex (MHC) molecules on the cell surface.MHC class IIPerosaminePMHC cellular microarray: PMHC cellular microarrays are a type of cellular microarray that has been spotted with pMHC complexes peptide-MHC class I or peptide-MHC class II.

(1/978) Locus specificity of polymorphic alleles and evolution by a birth-and-death process in mammalian MHC genes.

We have conducted an extensive phylogenetic analysis of polymorphic alleles from human and mouse major histocompatibility complex (MHC) class I and class II genes. The phylogenetic tree obtained for 212 complete human class I allele sequences (HLA-A, -B, and -C) has shown that all alleles from the same locus form a single cluster, which is highly supported by bootstrap values, except for one HLA-B allele (HLA-B*7301). Mouse MHC class I loci did not show locus-specific clusters of polymorphic alleles. This was considered to be because of either interlocus genetic exchange or the confusing designation of loci in different haplotypes at the present time. The locus specificity of polymorphic alleles was also observed in human and mouse MHC class II loci. It was therefore concluded that interlocus recombination or gene conversion is not very important for generating MHC diversity, with a possible exception of mouse class I loci. According to the phylogenetic trees of complete coding sequences, we classified human MHC class I (HLA-A, -B, and -C) and class II (DRB1) alleles into three to five major allelic lineages (groups), which were monophyletic with high bootstrap values. Most of these allelic groups remained unchanged even in phylogenetic trees based on individual exons, though this does not exclude the possibility of intralocus recombination involving short DNA segments. These results, together with the previous observation that MHC loci are subject to frequent duplication and deletion, as well as to balancing selection, indicate that MHC evolution in mammals is in agreement with the birth-and-death model of evolution, rather than with the model of concerted evolution.  (+info)

(2/978) HLA and HIV-1: heterozygote advantage and B*35-Cw*04 disadvantage.

A selective advantage against infectious disease associated with increased heterozygosity at the human major histocompatibility complex [human leukocyte antigen (HLA) class I and class II] is believed to play a major role in maintaining the extraordinary allelic diversity of these genes. Maximum HLA heterozygosity of class I loci (A, B, and C) delayed acquired immunodeficiency syndrome (AIDS) onset among patients infected with human immunodeficiency virus-type 1 (HIV-1), whereas individuals who were homozygous for one or more loci progressed rapidly to AIDS and death. The HLA class I alleles B*35 and Cw*04 were consistently associated with rapid development of AIDS-defining conditions in Caucasians. The extended survival of 28 to 40 percent of HIV-1-infected Caucasian patients who avoided AIDS for ten or more years can be attributed to their being fully heterozygous at HLA class I loci, to their lacking the AIDS-associated alleles B*35 and Cw*04, or to both.  (+info)

(3/978) HLA alleles determine human T-lymphotropic virus-I (HTLV-I) proviral load and the risk of HTLV-I-associated myelopathy.

The risk of disease associated with persistent virus infections such as HIV-I, hepatitis B and C, and human T-lymphotropic virus-I (HTLV-I) is strongly determined by the virus load. However, it is not known whether a persistent class I HLA-restricted antiviral cytotoxic T lymphocyte (CTL) response reduces viral load and is therefore beneficial or causes tissue damage and contributes to disease pathogenesis. HTLV-I-associated myelopathy (HAM/TSP) patients have a high virus load compared with asymptomatic HTLV-I carriers. We hypothesized that HLA alleles control HTLV-I provirus load and thus influence susceptibility to HAM/TSP. Here we show that, after infection with HTLV-I, the class I allele HLA-A*02 halves the odds of HAM/TSP (P < 0.0001), preventing 28% of potential cases of HAM/TSP. Furthermore, HLA-A*02(+) healthy HTLV-I carriers have a proviral load one-third that (P = 0.014) of HLA-A*02(-) HTLV-I carriers. An association of HLA-DRB1*0101 with disease susceptibility also was identified, which doubled the odds of HAM/TSP in the absence of the protective effect of HLA-A*02. These data have implications for other persistent virus infections in which virus load is associated with prognosis and imply that an efficient antiviral CTL response can reduce virus load and so prevent disease in persistent virus infections.  (+info)

(4/978) Engagement of natural cytotoxicity programs regulates AP-1 expression in the NKL human NK cell line.

NK cell cytotoxicity is a fast and efficient mechanism of target cell lysis. Using transcription analysis, such as multiplex messenger assays, we show here that natural cytotoxicity exerted by the human NKL cell line correlates with mRNA accumulation of very early activator protein (AP)-1 transcription factor genes such as JunB, FosB and c-Fos. In addition, DNA-binding activities of Jun-Fos heterodimers were observed by electrophoretic mobility shift assays during the course of natural cytotoxicity. Interaction between immunoglobulin-like transcript-2/leukocyte Ig-like receptor 1 on NKL cells and HLA-B27 on target cells leads to an impairment of NKL natural cytotoxicity, which correlates with an absence of JunB, FosB, and c-Fos transcription, as well as an absence of their DNA-binding activity. Our studies thus indicate that, despite the rapidity of NK cell-mediated lysis, AP-1 transcription factor is activated during the early stage of NK cell cytolytic programs and that engagement of NK cell inhibitory receptors for MHC class I molecules impairs the very early activation of AP-1.  (+info)

(5/978) Differences in gene conversion rates among exons between HLA-A and HLA-B loci.

To examine whether gene conversion occurs between two homologous loci of HLA-A and HLA-B, DNA sequences were compared and the differences or the numbers of substitutions per site at synonymous and nonsynonymous sites were calculated in the coding region and in the non-coding region. (1) Totally differences at synonymous sites in introns and coding regions are small as compared with the differences in the 5' flanking region. This indicates that gene conversion should occur between HLA-A and HLA-B loci. (2) In exon2 and exon3, the differences at synonymous sites are smaller than at nonsynonymous sites. This suggests that these exons are subject to positive natural selection, which is consistent with the reports of Hughes and Nei [1,2], because exon2 and exon3 encode alpha 1 and alpha 2 domains of the HLA molecule respectively which include mainly the antigen recognition sites (ARS). (3) in exon4, the difference at the synonymous site is the same as that in the 5' flanking region, which suggests that gene conversion does not frequently occur. The difference in this exon is extremely small at the nonsynonymous sites. This exon encodes the alpha 3 domain which does not have the antigen recognition sites but have an important function in maintaining the structure of the HLA molecule. From the above results, it can be concluded that gene conversion between HLA-A and HLA-B occurs more frequently in the two exons, exon2 and exon3 which have ARS regions. Furthermore, to examine a possibility that the variability of GC content along sequence influences the difference, the GC content was calculated along the sequence.  (+info)

(6/978) The MICA-A9 triplet repeat polymorphism in the transmembrane region confers additional susceptibility to the development of psoriatic arthritis and is independent of the association of Cw*0602 in psoriasis.

OBJECTIVE: To investigate the relative contribution of HLA antigens in the susceptibility to psoriasis and to localize additional genetic factors involved in psoriatic arthritis (PsA). METHODS: DNA from 45 patients with psoriasis, 65 with PsA, and 177 healthy control subjects was examined by polymerase chain reaction (PCR) using sequence-specific oligonucleotide probes to determine HLA-C. To examine whether MICA (class I major histocompatibility complex chain-related gene A) confers additional susceptibility, trinucleotide repeat polymorphism in the transmembrane region of the MICA gene was investigated by radioactive PCR. Further analysis of MICA was made by PCR-single-strand conformational polymorphism to determine the allelic variant corresponding to MICA transmembrane polymorphism. RESULTS: Our results reveal new findings: 1) the frequency of the Cw*0602 allele was significantly increased in both patient groups: psoriasis (corrected P [Pcorr] < 10(-5), relative risk [RR] 6.2), PsA (Pcorr < 10(-6), RR 6.3), 2) the trinucleotide repeat polymorphism MICA-A9 was present at a significantly higher frequency in PsA patients (Pcorr < 0.00035, RR 3.2), whereas a similar distribution was found in both the control and psoriasis population, 3) this polymorphism corresponds to the MICA-002 allele and was found to be overrepresented in patients with the polyarticular form (Pcorr < 0.0008, RR 9.35), 4) the increase in MICA-A9 in PsA patients is independent of linkage disequilibrium with Cw*0602, 5) this allele confers additional relative risk (RR 3.27, etiologic fraction 0.44; etiologic fraction is the proportion of disease cases among the total population that are attributable to 1 allele when the relative risk is > 1) in PsA patients who carry Cw*0602. CONCLUSION: The data obtained in this study are consistent with the polygenic inheritance of psoriasis. Cw*0602 appears to be the stronger genetic susceptibility factor for psoriasis. Independent of the HLA-C association, MICA-A9 polymorphism corresponding to the MICA-002 allele is a possible candidate gene for the development of PsA.  (+info)

(7/978) HLA-B15 peptide ligands are preferentially anchored at their C termini.

Therapies to elicit protective CTL require the selection of pathogen- and tumor-derived peptide ligands for presentation by MHC class I molecules. Edman sequencing of class I peptide pools generates "motifs" that indicate that nonameric ligands bearing conserved position 2 (P2) and P9 anchors provide the optimal search parameters for selecting immunogenic epitopes. To determine how well a motif represents its individual constituents, we used a hollow-fiber peptide production scheme followed by the mapping of endogenously processed class I peptide ligands through reverse-phase HPLC and mass spectrometry. Systematically mapping and characterizing ligands from B*1508, B*1501, B*1503, and B*1510 demonstrate that the peptides bound by these B15 allotypes i) vary in length from 7 to 12 residues, and ii) are more conserved at their C termini than their N-proximal P2 anchors. Comparative peptide mapping of these B15 allotypes further pinpoints endogenously processed ligands that bind to the allotypes B*1508, B*1501, and B*1503, but not B*1510. Overlapping peptide ligands are successful in binding to B*1501, B*1503, and B*1508 because these B15 allotypes share identical C-terminal anchoring pockets whereas B*1510 is divergent in the C-terminal pocket. Therefore, endogenous peptide loading into the B15 allotypes requires that a conserved C terminus be anchored in the appropriate specificity pocket while N-proximal anchors are more flexible in their location and sequence. Queries for overlapping and allele-specific peptide ligands may thus be contingent on a conserved C-terminal anchor.  (+info)

(8/978) Biosynthesis of HLA-C heavy chains in melanoma cells with multiple defects in the expression of HLA-A, -B, -C molecules.

Recent investigations have shown that malignant transformation may down-regulate the expression of class I HLA molecules, beta2-microglobulin (beta2m) and members of the antigen-processing machinery. In the present study, we HLA-genotyped and identified at a biochemical level the three (HLA-A25, -B8, -Cw7) class I alleles expressed by the previously described [D'Urso CM et al (1992) J Clin Invest 87: 284-292] beta2m-defective human melanoma FO-1 cell line and tested their ability to interact with calnexin, calreticulin and the TAP (transporter associated with antigen processing) complex. All these alleles were found to bind calnexin, but not calreticulin or the poorly expressed TAP complex, both in parental and beta2m-transfected FO-1 cells, demonstrating a complex defect of class I expression in FO-1 cells. In these conditions, Cw7 heavy chains interacted with calnexin more strongly than A25 and B8, and preferentially accumulated in the endoplasmic reticulum, in both a calnexin-associated and a calnexin-free form. In addition, they could be transported to the cell surface at low levels even in the absence of beta2m, without undergoing terminal glycosylation. These results establish a parallel between HLA-C and the murine Db and Ld molecules which have been found to be surface expressed and functional in beta2m-defective cells. They also demonstrate distinctive features of HLA-C molecules. We propose that the accumulation of several assembly intermediates of HLA-C might favour the binding of peptide antigens not readily bound by HLA-A and -B molecules in neoplastic cells with suboptimal class I expression.  (+info)



Tissue Antigens


alleles


  • To confirm the correlation of HLA-DRB1 and HLA-DQB1 alleles and haplotypes with HBV antibody concentrations and antibody decay kinetics in vaccinated adolescents. (clinicaltrials.gov)
  • This laboratory-based substudy of ATN 024 and 025 will evaluate the genetic contribution to highly individualized immune responses to hepatitis B vaccine in individuals and confirm the correlation of specific human leukocyte antigen (HLA) alleles and haplotypes with Hepatitis B Virus (HVB) antibody concentrations and antibody decay kinetics in vaccinated adolescents. (clinicaltrials.gov)
  • Disease susceptibility for type 1 diabetes is strongly associated with the inheritance of specific HLA alleles. (diabetesjournals.org)
  • However, conventional allele frequency analysis can miss HLA associations because many alleles are rare. (diabetesjournals.org)
  • In addition, analysis of HLA susceptibility is confounded because disparate HLA alleles may share peptide-binding motifs, often referred to as shared epitopes. (diabetesjournals.org)
  • Conventional frequency analysis of the HLA alleles associated with diabetes is limited because it does not account for these HLA shared epitopes. (diabetesjournals.org)

molecules


  • An effective and effecient peptide binding prediction approach for a broad set of HLA-DR molecules based on ordered weighted averaging of binding pocket profiles. (ebi.ac.uk)
  • Engagement of the T cell receptor molecules with MHC-antigen complexes presented by B cells ascertains antigen specificity in T cell-dependent help. (biomedsearch.com)
  • Ligation of MHC molecules on the surface of B cells, however, has not only been implicated in antigen-specific T-B cell interaction, but has also been linked to the induction of B cell apoptosis. (biomedsearch.com)
  • Class II molecules are expressed in antigen presenting cells (APC: B lymphocytes, dendritic cells, macrophages). (genecards.org)
  • Exogenous antigens that have been endocytosed by the APC are thus readily available for presentation via MHC II molecules, and for this reason this antigen presentation pathway is usually referred to as exogenous. (genecards.org)
  • To produce a MHC class II molecule that presents an antigen, three MHC class II molecules (heterodimers of an alpha and a beta chain) associate with a CD74 trimer in the ER to form a heterononamer. (genecards.org)
  • HLA-DM stabilizes MHC class II molecules until primary high affinity antigenic peptides are bound. (genecards.org)
  • In B-cells, the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO. (genecards.org)
  • Lysosomal microenvironment has been implicated in the regulation of antigen loading into MHC II molecules, increased acidification produces increased proteolysis and efficient peptide loading. (genecards.org)
  • They are mostly found in the highly polymorphic antigen-binding groove of HLA class I and class II molecules. (diabetesjournals.org)
  • Class I molecules (HLA-A, -B, and -C) present endogenous peptides to CD8 + T cells. (diabetesjournals.org)
  • Class II molecules (HLA-DR, -DQ, and -DP) are heterodimers that present exogenous peptides to CD4 + T cells and have four major pockets comprising polymorphic β-chain amino acids in conjunction with α-chain residues ( 11 ). (diabetesjournals.org)

peptides


  • Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells. (genecards.org)
  • The repertoire of peptides that can bind in the peptide-binding groove for each HLA allele is determined by the amino acids that line the pockets. (diabetesjournals.org)

Antibody


  • B cells interacting with the second subset of T cells did not differentiate into antibody-secreting cells, but underwent apoptosis. (biomedsearch.com)
  • All eligible youths must be negative for HBV core antibody, HBV surface antigen, and HBV surface antibody at the time of enrollment in to ATN 024. (clinicaltrials.gov)
  • The antibody reacts with a combinatorial determinant of the HLA A,B,C - beta-2-microglobulin complex. (atcc.org)

dendritic cells


  • Primary dendritic cells (DCs) also to express HLA-DO. (genecards.org)

disparate


  • Of the 15 recipients of 2 and 3 antigen disparate haploidentical transplants, 12 were evaluable for GVHD (3 died of graft failure). (knowcancer.com)

Genes


  • To determine if other genetic variations (768 single nucleotide polymorphisms (SNP) in about 50 genes) in the immune response pathways can confer additional effects on immune responses to hepatitis B vaccination. (clinicaltrials.gov)

exogenous


  • As membrane proteins on their way to degradation in lysosomes as part of their normal turn-over are also contained in the endosomal/lysosomal compartments, exogenous antigens must compete with those derived from endogenous components. (genecards.org)

loci


  • The match may be determined at serologic level for HLA-A and HLA-B loci. (knowcancer.com)
  • To identify the HLA shared epitopes associated with diabetes, we analyzed high-resolution genotyping for class I and class II loci. (diabetesjournals.org)

Major Histoco


  • HLA-DPB1 (Major Histocompatibility Complex, Class II, DP Beta 1) is a Protein Coding gene. (genecards.org)

epitopes


  • Two novel mesothelin HLA-A2 epitopes were defined. (aacrjournals.org)
  • Potential CTL epitopes of mesothelin specific for HLA-A2, HLA-A3, and HLA-A24 have recently been reported. (aacrjournals.org)
  • CD8 + T-cell responses to these HLA-A2, HLA-A3, and HLA-A24 epitopes were detected in patients vaccinated with granulocyte macrophage-colony stimulating factor-transduced pancreatic cancer cell lines ( 24 ). (aacrjournals.org)
  • The HLA epitopes most strongly associated with susceptibility for disease were DQB1 A 57 , DQA1 V 76 , DRB1 H 13 , and DRB1 K 71 , whereas DPB1 YD 9,57 , HLA-B C 67 , and HLA-C YY 9,116 were more weakly associated. (diabetesjournals.org)
  • The HLA epitopes strongly associated with resistance were DQB1 D 57 , DQA1 Y 80 , DRB1 R 13 , and DRB1 A 71 . (diabetesjournals.org)
  • The prevalence of both DQ and DR susceptibility epitopes was higher in patients than in control subjects and was not exclusively a result of linkage disequilibrium, suggesting that multiple HLA epitopes may work together to increase the risk of developing diabetes. (diabetesjournals.org)
  • Thus, a systematic analysis of all possible HLA class I and class II epitopes should provide a better understanding of genetic susceptibility for type 1 diabetes. (diabetesjournals.org)
  • HLA epitopes can be single amino acids or groups of contiguous or noncontiguous amino acids. (diabetesjournals.org)
  • These polymorphic amino acid residues can potentially combine to form millions of different HLA epitopes. (diabetesjournals.org)
  • We have developed the HLA Epitope Analysis Program (HEAP) to analyze the millions of shared HLA epitopes comprising one to four noncontiguous amino acids between patient and control populations. (diabetesjournals.org)

donor


  • Unfortunately only about 30% of patients who could benefit from this procedure have a HLA-matched related donor (MRD), and only an additional 20% can find a suitable HLA-matched unrelated donor (MUD) 1. (knowcancer.com)
  • ease of procurement, lack of donor attrition, absence of risk to mothers and donors, potential reduced risk of GVHD, and less stringent criteria for HLA matching 2. (knowcancer.com)
  • Must have a 5 or 6 of 6 human leukocyte antigens (HLA)-matched donor. (knowcancer.com)

polymorphism


  • The HLA-DR polymorphism is found in the β-chain because the α-chain is effectively conserved in the peptide-binding region. (diabetesjournals.org)

susceptibility


  • A dominant resistance phenotype was observed for individuals bearing a protective HLA epitope, even in the presence of a susceptibility epitope. (diabetesjournals.org)

hepatitis


  • This laboratory-based substudy of an effectiveness trial of two Hepatitis B vaccines in HIV-negative youths is being done to evaluate the genetic contribution to the individualized immune response. (clinicaltrials.gov)

class


  • HLA-DPB belongs to the HLA class II beta chain paralogues. (genecards.org)
  • Soon after the entry of this complex into the endosomal/lysosomal system where antigen processing occurs, CD74 undergoes a sequential degradation by various proteases, including CTSS and CTSL, leaving a small fragment termed CLIP (class-II-associated invariant chain peptide). (genecards.org)
  • More than 40 genetic linkages have been associated with this disease, but linkage to HLA class II is the most dominant ( 1 ). (diabetesjournals.org)

immunoglobulin


  • To examine the role of T helper cells in either induction of immunoglobulin synthesis or B cell apoptotic death, we have facilitated T cell receptor-MHC interaction through a bacterial superantigen. (biomedsearch.com)
  • the addition of the superantigen suppressed immunoglobulin production in B cells activated by anti-CD3-stimulated helper T cells, indicating that the T cells delivered an apoptotic signal to the B cell. (biomedsearch.com)

Immune Response


  • Acute rejection develops as a consequence of the recognition of nonself histocompatibility antigens and elaboration of an immune response against allogeneic heart muscle that leads to compromised cardiac function and graft loss. (ahajournals.org)

molecular


  • Brodsky FM, Parham P. Monomorphic anti-HLA-A,B,C monoclonal antibodies detecting molecular subunits and combinatorial determinants. (atcc.org)

Induction


  • Induction of B cell apoptosis by TH0, but not TH2, CD4+ T cells. (biomedsearch.com)
  • Induction of B cell apoptosis was a feature of T cells with a TH0 lymphokine pattern. (biomedsearch.com)

expression


  • Direct demonstration of increased expression of Thomsen-Friedenreich (TF) antigen in colonic adenoca. (biomedsearch.com)

cells


  • T cell clones providing effective MHC restrictive B cell help could be distinguished from T cells facilitating B cell apoptosis based on their lymphokine secretion profile. (biomedsearch.com)
  • Mesothelin, a glycosylphosphatidylinositol-linked glycoprotein, is a differentiation antigen of mesothelial cells. (aacrjournals.org)
  • Medullary epithelial cells of the thymus express self antigens in the context of MHC I and II. (freezingblue.com)

peptide


  • GO annotations related to this gene include peptide antigen binding . (genecards.org)

human


  • Horejsí V, Nĕmec M, Angelisová P, Kristofová H, Gorga JC, Hilgert I. Characterization of seven new monoclonal antibodies against human DR, DR + DP and DQ1 + DQ3 antigens. (acris-antibodies.com)
  • Thisa ntibody recognizes common epitope on beta-chain of human HLA-DR and HLA-DP. (acris-antibodies.com)

Complex


  • The removal of CLIP is facilitated by HLA-DM via direct binding to the alpha-beta-CLIP complex so that CLIP is released. (genecards.org)

surface


  • A cell surface receptor that signals a common lymphoid progenitor cell to differentiate into a T cell lineage and not a B cell one. (freezingblue.com)

Acute


  • Acute GVHD has occurred very infrequently in recipients of HLA-matched and HLA-1 antigen mismatched UCB SCT. (knowcancer.com)

cell


  • CD4+ T cell clones could be categorized into two clearly distinct subsets based upon their ability to promote B cell help in the presence of superantigen. (biomedsearch.com)
  • Promotion of MHC-restricted B cell help was associated with a TH2 lymphokine profile. (biomedsearch.com)

patients


  • Twenty patients received HLA 1-3 antigen mismatched grafts. (knowcancer.com)

shown


  • A number of studies have shown that HLA-DRB1*03:01, *04:01, *04:02, and *04:05 are most strongly linked to diabetes, whereas DRB1*04:03 is resistant. (diabetesjournals.org)