Thymic selection of natural killer-1+ natural T cells that express alpha beta T cell receptors requires a conserved beta 2-microglobulin-associated molecule, presumably CD1d, displayed by CD4+8+ thymocytes. Here we demonstrate that positive selection of natural T cells occurs independent of transporters associated with antigen presentation-1 (TAP-1) function. Moreover, natural T cells in TAP-1o/o mice are numerically expanded. Several H-2 class Ib molecules function in a TAP-independent manner, suggesting that if expressed in TAP-1o/o thymocytes, they could play a role in natural T cell development. Of these class Ib molecules, H-2TL is expressed by TAP-1o/o thymocytes. Moreover, we find that thymi of TL+ mice congenic or transgenic for H-2T18 also have a numerically expanded natural T cell repertoire compared with TL- mice. This expansion, as in TAP-1o/o thymi, is evident in each of the limited T cell receptor V beta chains expressed by natural T cells, suggesting that TL and CD1d impact ...
Implantation of pieces of human fetal liver and thymus into SCID mice results in the development of a human thymus-like organ, in which sustained lymphopoiesis is reproducibly observed. In this model, T cell development can be experimentally manipulated. To study the influence of thymic selection on the development of the human T cell repertoire, the T cell receptor (TCR) V beta gene repertoire of double-positive (CD4+CD8+) and single-positive (CD4+CD8- and CD4-CD8+) T cells was analyzed in the SCID-hu thymus using a multiprobe ribonuclease protection assay. TCR diversity in double-positive SCID-hu thymocytes was found to be comparable with that present in the thymus of the fetal liver donor, did not change with time, and was independent of the origin of the thymus donor. Thymic selection in SCID-hu thymus induces changes in V beta usage by the single-positive CD4+ or CD8+ T cells comparable with those previously reported for single-positive cells present in a normal human thymus. Finally, ...
Whereas most T cells express surface CD4 or CD8 molecules, a minority lacks both. CD4-8- cells usually express the gamma delta T-cell receptor, but here we describe a population of CD4-8- T cells from the peripheral blood that express the alpha beta heterodimer. These cells have different surface antigens than gamma delta+ T cells, expressing CD5 but lacking CD16, and differ in function from gamma delta+ T cells. CD4-8- alpha beta+ cells lack non-major histocompatibility complex-restricted cytolytic function but can be induced to lyse their target cells after activation of their T-cell receptors. A peculiar characteristic of these cells is their responsiveness to interleukin 3. Since these cells have not altered their phenotype or function over a 12-month period in culture, they appear to be mature T cells. The results indicate that normal human peripheral blood contains two subsets of CD4-8- T cells, expressing either gamma delta or alpha beta receptors, that differ in function, phenotype, and growth
CD4-CD8- (double negative [DN]) alpha/beta T cells are a largely uncharacterized subpopulation of unknown function. To investigate whether these cells are selected to recognize particular antigens or antigen-presenting molecules, DN alpha/beta T cells were purified from the peripheral blood of five normal donors and their T cell receptor (TCR) alpha and beta chains were examined. Random cloning of TCR alpha chains by single-sided polymerase chain reaction (PCR) amplification identified an invariant rearrangement between V alpha 24 and J alpha Q, with no N region diversity, which was expressed preferentially by DN alpha/beta T cells from all donors. Random cloning also identified a precise V alpha 7.2-J alpha (IGRJa14) rearrangement, with two variable amino acids encoded in the V-J junction, which was enriched in the DN alpha/beta T cell preparations from some, but not all, donors. Analysis of TCR beta chains by quantitative PCR amplification demonstrated that the expression of four V beta gene ...
The T cell receptor (TCR) V beta-determining region of two bacterial superantigens, staphylococcal enterotoxin A (SEA) and SEE, has been mapped to the COOH-terminal region of SEA and SEE using a panel of recombinant SEA/SEE hybrids. Total TCR V beta mRNA enrichment in human peripheral blood T cell cultures was determined by a novel single-tube amplification technique using a redundant V beta-specific primer. SEA routinely enriched mRNA coding for hV beta 1.1, 5.3, 6.3, 6.4, 6.9, 7.3, 7.4, and 9.1, while SEE, which is 83% homologous to SEA, enriched hV beta 5.1, 6.3, 6.4, 6.9, and 8.1 mRNA. Exchanging residues 206 and 207 was sufficient to convert in toto the TCR V beta response of human peripheral T lymphocytes. In addition, an SEA-reactive murine T cell line, SO3 (mV beta 17), unresponsive to wild-type SEE responded to SEE-S206N207, while an SEE-specific human T cell line, Jurkat (hV beta 8.1), unresponsive to SEA was stimulated strongly by SEA-P206D207. Exchanging all other regions of SEA and ...
The mechanism of T cell depletion during infection with the human immunodeficiency virus (HIV) is unclear. Examination of the repertoire of T cell receptor V (variable) regions in persons infected with HIV revealed the absence of a common set of V beta regions, whereas V alpha usage was normal. The lack of these V beta segments did not appear to correlate with opportunistic infections. The selective elimination of T cells that express a defined set of V beta sequences may indicate the presence of an HIV-encoded superantigen, similar to those encoded by the long terminal repeat of the mouse mammary tumor virus. ...
Polymerase chain reaction (PCR) technology was employed to examine peripheral blood and synovial T cells in patients with rheumatoid arthritis (RA) for biased utilization of T cell receptor (TCR) variable region (V) genes. Oligonucleotide primers specific for individual TCR V beta gene families were used to amplify TCR gene products in a semiquantitative assay of their relative utilization in unselected T cell populations. Mean V beta expression in 24 RA peripheral blood samples was very similar to that in a panel of 15 normal subjects, except for a slight decrease in V beta 13.2 expression. V beta utilization in 8 RA synovial tissue samples and 13 synovial fluid samples was compared to simultaneously obtained blood samples. Although heterogeneous patterns of skewed V beta utilization were observed, several significant trends emerged. By a number of approaches to data analysis, a statistically significant increase in expression of V beta 6 and V beta 15 in synovial T cells was documented. In ...
Purchase quality tested T cell receptor Alpha + Beta antibodies at Immuquest. Quality T cell receptor Alpha + Beta antibodies are available online from technical experts in production
Sarcoidosis is a chronic noncaseating granulomatous disease of unknown etiology. An accumulation of CD4+ T cells in the alveolar space of the lungs is a characteristic feature of the disease. We have in this study analyzed T-cell receptor (TCR) variable region (V) gene usage by CD4+ and CD8+ lung and peripheral blood T cells of 29 sarcoidosis patients and 15 control subjects. In the patient group, we found a 100% positive correlation between TCR V alpha 2.3+ CD4+ lung T-cell expansions and the expression of the HLA-DR3(17),DQ2 haplotype. The remaining TCR V alpha/V beta gene products analyzed in this study--V alpha 12, V beta 2, V beta 3, V beta 5.1, V beta 5.2/5.3, V beta 5.3, V beta 6.7, V beta 8.1, and V beta 12--were in general normally expressed by CD4+ T cells, although some of them were used to a significantly higher or lower degree by lung T cells compared to peripheral blood T cells. We also performed repeated TCR V gene analyses on some HLA-DR3+ patients and found an association ...
ABSTRACT. Novel aspects of T cells containing TCRVβ20-1 are numerous, ranging from pathogen specific reactivity to specific tissue homing, or possible T cell subsets. Recently, it was demonstrated that TCR itself could become reactive by binding to small molecules free of the pHLA interface. Our work here was to identify a natural ligand binding to an identified pocket on the CDR2β loop of these TCR. Using docking of suspected ligands, we were able to show Guanine and Adenine diand tri-nucleotides readily bind to the identified site. Comparing these with small molecule sites found on other TCR types, we show this interaction is novel. With further molecular dynamic simulations, these sites are shown to be plausible by conducting simple computational based solubility tests as cross validation. Combined with simple proliferative responses, the identified nucleotides are also shown to have functional consequences by inducing T cell proliferation for CD4/Vβ20-1 + T cells, while failing to induce ...
ABSTRACT McMILLAN, RUTH ERICA. Transcriptional Control of D?2. (Under the direction of Michael L. Sikes). The immune system?s response to invading pathogens depends on the ability of T and B-lymphocytes to generate a diverse repertoire of antigen receptors. This diversity is created during lymphocyte development by somatic recombination of variable (V), diversity (D) and joining (J) gene segments. Transcription of unrearranged gene segments precedes their recombination. Given the correlation of transcription and recombination, it has been suggested that enhancers and promoters within each locus may regulate the recombinational accessibility of nearby gene segments. For example, in developing T cells, two stages of recombination (first D to J, then V to DJ) are seen in the T cell receptor beta gene (TCR?). Both steps require the TCR? enhancer, E?, while a promoter associated with the first D segment (PD?1) only controls its recombination. In mutant cells that lack PD?1, the second D? rearranges ...
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In patient 13, the T cell receptor Vβ repertoire was investigated by flow cytometry in two sentinel (nodes at the day of operation and after in vitro cell cult
1J8H: Structure of a complex of the human alpha/beta T cell receptor (TCR) HA1.7, influenza hemagglutinin peptide, and major histocompatibility complex class II molecule, HLA-DR4 (DRA*0101 and DRB1*0401): insight into TCR cross-restriction and alloreactivity.
T cell receptor antigen complex. Molecular model of the alphabeta T cell receptor bound to the influenza haemagglutinin antigen and MHC class II molecule HLA-DR1. T cell receptors are protein complexes found on the surface of a type of white blood cell called T lymphocytes (or T cells), part of the bodys immune system. Antigens (foreign proteins) are presented to T cell receptors by MHC molecules to effect an immune response. - Stock Image C025/1593
OBJECTIVE: To investigate the hypothesis that clonality of synovial T cells from patients with rheumatoid arthritis is at least partly due to the presence of virus-specific T cells expressing a restricted repertoire of T cell receptors (TCRs). METHODS: Using fluorescently labeled HLA class I-peptide tetramers, populations of virus-specific CD8+ T cells were identified in samples of peripheral blood and synovial fluid taken from 4 patients with inflammatory arthritis. The TCR repertoire of the virus-specific T cells in the synovial fluid was analyzed using a panel of TCR beta variable region-specific monoclonal antibodies. Where T cells expressing a particular Vbeta chain dominated the response to a viral epitope, the sequences of these Vbeta chains were derived from sorted populations of antigen-specific T cells by reverse transcription-polymerase chain reaction. RESULTS: CD8+ T cells specific for Epstein-Barr virus, cytomegalovirus, and influenza virus were enriched in synovial fluid compared with
1fyt: Structure of a covalently stabilized complex of a human alphabeta T-cell receptor, influenza HA peptide and MHC class II molecule, HLA-DR1.
Invariant human TCR Valpha24-Jalpha18+/Vbeta11+ NKT cells (iNKT) are restricted by CD1d-alpha-glycosylceramides. We analyzed crystal structures and binding characteristics for an iNKT TCR plus two CD1d-alpha-GalCer-specific Vbeta11+ TCRs that use different TCR Valpha chains. The results were similar to those previously reported for MHC-peptide-specific TCRs, illustrating the versatility of the TCR platform. Docking TCR and CD1d-alpha-GalCer structures provided plausible insights into their interaction. The model supports a diagonal orientation of TCR on CD1d and suggests that complementarity determining region (CDR)3alpha, CDR3beta, and CDR1beta interact with ligands presented by CD1d, whereas CDR2beta binds to the CD1d alpha1 helix. This docking provides an explanation for the dominant usage of Vbeta11 and Vbeta8.2 chains by human and mouse iNKT cells, respectively, for recognition of CD1d-alpha-GalCer.
TCR V beta 11, APC, clone: RR3-15, eBioscience™ 100μg; APC TCR V beta 11, APC, clone: RR3-15, eBioscience™ Primary Antibodies V
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1KB5: The three-dimensional structure of a T-cell antigen receptor V alpha V beta heterodimer reveals a novel arrangement of the V beta domain.
T Cell Receptor (TCR) alpha/beta, 100 Tests. The antigen-specific T cell receptor (TCR) is composed of either alpha and beta subunit, or gamma and delta subunit.
TCR-gene-transfer is an efficient strategy to produce therapeutic T cells of defined antigen specificity. However, there are substantial variations in the cell surface expression levels of human TCRs, which can impair the function of engineered T cells. Here we demonstrate that substitutions of 3 amino acid residues in the framework of the TCR variable domains consistently increase the expression of human TCRs on the surface of engineered T cells.The modified TCRs mediate enhanced T cell proliferation, cytokine production and cytotoxicity, while reducing the peptide concentration required for triggering effector function up to 3000-fold. Adoptive transfer experiments in mice show that modified TCRs control tumor growth more efficiently than wild-type TCRs. Our data indicate that simple variable domain modifications at a distance from the antigen-binding loops lead to increased TCR expression and improved effector function. This finding provides a generic platform to optimize the efficacy of TCR ...
The SMARTer Human TCR a/b Profiling Kit enables users to perform T-cell receptor repertoire analysis from human RNA samples or directly from cells.
The SMARTer Human TCR a/b Profiling Kit enables users to perform T-cell receptor repertoire analysis from human RNA samples or directly from cells.
Long-range Trbv looping to 5′PC requires an RC barrier element. (A) Expression of Prss2 transcripts were measured by RT-qPCR relative to Actb in DN thymocytes
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TY - JOUR. T1 - Radiation leukemia virus-induced T-cell lymphomas with common T-cell receptor variable region structure and similar binding specificity for retrovirus. AU - ONeill, H C. PY - 1991/11. Y1 - 1991/11. N2 - The 5C2 cell line was derived following culture of mouse spleen cells exposed in vivo and in vitro to radiation leukemia virus (RadLV) containing supernatants from the C6VL/1 T cell lymphoma. This cell line has been found to express an alpha beta T-cell receptor (TCR) identifiable with the Mab124-40 anti-clonotypic antibody which is specific for C6VL/1. It has been shown to be genetically and phenotypically distinct from C6VL/1 with a unique phenotype, i.e. CD4-, CD8-, CD3+, TCR-alpha beta. 5C2 has been shown to express high levels of alpha and beta chain mRNA and to utilize the same or similar V alpha and V beta region genes as C6VL/1. Whereas C6VL/1 binds cross-reactively to both RadLV/C6VL and an unrelated isolate RadLV/VL3, 5C2 has binding specificity for only RadLV/C6VL, ...
BACKGROUND: The principal symptoms of myasthenia gravis (MG), muscle weakness and fatigue due to impaired neuromuscular transmission, are caused by autoantibodies to the muscle nicotinic acetylcholine receptor (AChR). The mechanisms underlying the autoimmune response, however, appear to be initiated by activation of specific HLA class II-restricted CD4+ T lymphocytes. Thus, central to elucidating the causation of MG is determining how T cells are recruited to contribute to misguided immunological assaults on the major autoantigenic target, AChR. MATERIALS AND METHODS: By combining a polymerase chain reaction (PCR)-based strategy and Southern blot technique, we have analyzed the frequency of expression of 22 individual T cell receptor (TCR) V beta gene subfamilies in CD4+ and CD8+ peripheral blood T cell subsets derived from eight MG patients and seven healthy controls. The quantification of relative usage of individual TCR J beta gene segments was performed by hybridization of PCR-amplified ...
T cell specificity emerges from a myriad of processes, ranging from the biological pathways that control T cell signaling to the structural and physical mechanisms that influence how TCRs bind peptides and MHC proteins. Of these processes, the binding specificity of the TCR is a key component. However, TCR specificity is enigmatic: TCRs are at once specific but also cross-reactive. Although long appreciated, this duality continues to puzzle immunologists and has implications for the development of TCR-based therapeutics. In this review, we discuss TCR specificity, emphasizing results that have emerged from structural and physical studies of TCR binding. We show how the TCR specificity/cross-reactivity duality can be rationalized from structural and biophysical principles. There is excellent agreement between predictions from these principles and classic predictions about the scope of TCR cross-reactivity. We demonstrate how these same principles can also explain amino acid preferences in ...
An experimental model of two interacting clones of T cells is described, which may be used for defining and exploring the T-cell immunoregulatory network. Mx9/9 is a CD4 clone bearing an antigen receptor recognized by the Mx9 anti-V beta 8 monoclonal antibody (MoAb). Anti-V beta 8 MoAbs activate and induce cell proliferation of this clone. Autologous clones were raised against Mx9/9 cells using the peripheral blood mononuclear (PBM) cells of the Mx9/9 clone donor (PBMjm). Some of these cloned anti-clone cells proliferated after stimulation with irradiated Mx9/9 cells, but not after stimulation with other autologous cloned T cells or heterologous PBM, suggesting that these clones recognize the T cell receptor (TCR) of the Mx9/9 cells. The proliferation of the Mx9/9 stimulated cloned anticlone cells was blocked by anti-class II MoAbs, indicating that the autoreactive clones recognize their target antigen in conjunction with HLA Class II products. The ability of clone Mx9/9 to proliferate after stimulation
TCR V beta 8b antibody [MX-6] (FITC) (T cell receptor beta locus) for FACS, ICC/IF, IHC-Fr, IP, Activation. Anti-TCR V beta 8b mAb (GTX79220) is tested in Human samples. 100% Ab-Assurance.
Material and methods Three DMARD-naïve ERA patients (disease duration , 1 year) and three ESRA patients (disease duration ,2 years) were included. All fulfilled the American College of Rheumatology1987 criteria for RA. mRNA was isolated from paired ST and PB samples. A linear amplification with primers for all V(ariable)-genes of the T cell receptor β-chain was performed. The amplified products contain the CDR3s of all T cells. Samples were processed using a Genome Sequencer (454) analysing up to 15 000 receptors per sample, The frequency of each clone was determined by its CDR3 frequency (% of all CDR3s analysed). Clones with a CDR3 frequency of ,1% were arbitrarily considered as highly expanded clones (HECs).. ...
The analysis of TCR repertoire is of high value to better understand the immune system. Flow cytometry quickly measures the proportional TCR-Vβ usage in multiple T cell subsets on a per-cell basis, without the need for cell-sorting 1. The IOTest Beta Mark TCR Vβ Repertoire Kit (IM3497) allows the assessment of 24 different TCR Vβ representing about 70% coverage of normal human TCR Vβ repertoire. It provides a snapshot of the diversity of the repertoire, percentage of each TCR Vβ among overall T cells or a specific subsets, and visibility on potential expansion of a specific clone. Taking advantage of the fact that Vβ specificities may be grouped into mutually exclusive combinations, the detection of 3 Vβ expressions in the same tube is possible with the use of an innovative staining strategy combining three monoclonal antibodies with only two fluorophores. Historically, the percentage of T cells expressing a given TCR Vβ chain was determined using flow cytometry analysis software and ...
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J Immunol 172:4709-4716, 2004. PMID: 15067046. Cascalho M, Platt JL. B cell-dependent T cell development. Acta Paediatr 93(Supplement 445):52-53, 2004. PMID: 15176721. Cascalho M, Platt JL. B cells and B cell products-helping to restore cellular immunity? Transfus Med Hemother 33:45-49, 2006. PMID: 16755301. Balin SJ, Cascalho M. The rate of mutation of a single gene. Nucleic Acids Res. 2010. 38:1575-82. PMID: 20007603 3. Fitness of cellular immunity and T cell receptor diversity. T cell diversity is generally thought to confer immune fitness. However which properties of immunity depend absolutely on TCR receptor diversity and the extent of diversity necessary for optimal function are not fully understood. My research conducted in collaboration with Dr. Platt revealed for the first time that significant contractions of the T cell receptor repertoire do not impair certain functions of cell-mediated immunity, such as defense against intracellular fungi and rejection of grafts disparate for minor ...
Next-generation sequencing enabled T-cell receptor (TCR) repertoire analysis has gained major attention in scientific as well as clinically driven research. However, despite improvements of sequencing technology, next-generation sequencers produce huge data sets that are usually prone to errors, thus urging the need for improved analysis tools being able to account not only for the large number of sequences but also for sequencing artifacts. TCRProfiler is a tool that includes sequencer generated quality values to improve reliability of TCR repertoire analysis. As a stand alone tool for parallel and detailed analysis, TCRProfiler delimits combinatorial diversity (rearranged germline V, (D), and J genes) and junctional diversity (P(alindromic)-, and N(on-template)-nucleotides) of TCR alpha and/or beta chain sequences. TCRProfiler generates probe-specific statistical repertoire profiles, as well as visualization files to allow fast and comprehensive accession of repertoire diversity. In a single ...
TCR alpha + TCR beta antibody [H57-597] (T-cell receptor alpha chain) for FACS, IHC-Fr, WB. Anti-TCR alpha + TCR beta mAb (GTX74978) is tested in Human, Mouse samples. 100% Ab-Assurance.
1. The regulation of the immune response: vaccine design, phage-based vaccines, Virus-like-particle vaccines, protein vaccines, Alzheimers Disease immunotherapy, induction of immune responses to self-antigens, correlates of vaccine efficacy, signaling in T cell development and activation, T cell receptor repertoire in Coeliac disease, T cell receptor repertoire of antigen-specific T cell lines ...
Complete information for TRBV30 gene (Protein Coding), T-Cell Receptor Beta Variable 30 (Gene/Pseudogene), including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Clone REA651 recognizes the mouse V beta 10 T cell receptor (TCR Vβ10). The T cell receptor is responsible for recognizing antigens bound to major histocompatibility complex (MHC) molecules. It is a disulfide-linked membrane-anchored heterodimeric glycoprotein normally consisting of the highly variable alpha and beta chains expressed as part of a complex with the invariant CD3 chain molecules. The α and β TCR chains are composed of constant and variable regions, each encoded by distinct gene segments. TCR Vβ10 is a variant of the TCR β chain and is expressed on T cells having the a haplotype, but not with the b and c haplotype of the TCRβ gene complex. Additional information: Clone REA651 displays negligible binding to Fc receptors. - Lëtzebuerg
In this report, we describe the molecular and functional characterization of T-cell clones identified in peripheral blood from patients with relapsed myeloma responding to DLI. These clones were initially identified through analysis of TCR Vβ repertoire (spectratyping), a technique that provides a comprehensive characterization of the circulating T-cell compartment (21 , 24 , 25) . Serial analysis of T-cell repertoire in patient samples has also been used to detect the emergence of oligoclonal and clonal T cells at different times in vivo (18 , 26 , 27) . By combining analysis of TCR repertoire with clinical events, we observed the expansion of individual T-cell clones in peripheral blood that were temporally associated with the initiation of either a GVM or GVHD response (17) . However, despite the association of these T-cell clones with specific clinical responses, the functional specificity of these T cells was not established. Further studies were therefore undertaken to quantify the ...
T Cell Receptor (TCR) V beta 4, 0.125 mg. The receptors on T cells consist of immunoglobulin like integral membrane glycoproteins containing 2 polypeptide subunits, alpha and beta, of similar molecular weight, 40 to 55 kD in the human.
There is considerable controversy about the mechanism of T cell receptor (TCR) triggering, the process by which the TCR tranduces signals across the plasma membrane after binding to its ligand (an agonist peptide complexed with an MHC molecule). Three main types of mechanism have been proposed, which involve aggregation, conformational change and segregation. Here, we review recently published evidence for each type of mechanism and conclude that all three may be involved. This complexity may reflect the uniquely demanding nature of TCR-mediated antigen recognition, which requires the detection of a very weak signal (very rare foreign peptide-MHC ligands) in the presence of considerable noise (abundant self peptide-MHC molecules).
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How the T cell receptor engages antigen is known, but not how that triggers intracellular signaling. The first direct support for a mechanism based on the spatial reorganization of signaling proteins, proposed 10 years ago and referred to as the kinetic-segregation model, is now beginning to emerge, along with indications that it may also apply to the triggering of nonclonotypic receptors. We describe here the development of the model, review new data and suggest how the model fits a broader conceptual framework for receptor triggering. We also consider the capacity of the model, versus that of other proposals, to account for the established features of TCR triggering. © 2006 Nature Publishing Group.
We have examined the interaction of the microbial superantigen staphylococcal enterotoxin A (SEA) with peptides corresponding to overlapping regions of the T-cell antigen receptor beta chain variable region V beta 3. SEA is known to stimulate murine T cells bearing certain V beta elements, among them V beta 3. Five peptides were synthesized representing amino acids 1-24, 20-44, 39-60, 57-77, and 74-95 of V beta 3. We demonstrate here that soluble V beta 3-bearing beta chains can bind to a complex of SEA and major histocompatibility complex class II and that the synthetic peptide V beta 3-(57-77) blocked this interaction. The peptide V beta 3-(57-77) also inhibited SEA-induced interferon-gamma production and SEA-induced proliferation of B10.BR spleen cells. Conversely, the peptide corresponding to amino acids 57-77 of V beta 8.2, a V beta element that is not recognized by SEA, decreased staphylococcal enterotoxin C-2-induced proliferation but did not affect SEA-induced proliferation. The peptide ...
Infection of people with human immunodeficiency virus (HIV) as well as LP- BM5 infection in mice results in progressive deterioration of the immune system in the majority of untreated hosts. Peptide immunotherapy has been shown to be effective in the stimulation or immunoregulation of T-helper 1 (TH1) and T-helper 2 (TH2) response subsets. In murine acquired immunodeficiency syndrome (AIDS), TH1 deficiency enables the host to be susceptible to coxsackievirus infection, inducing cardiopathology in a short period. T-cell receptor (TCR) V 8.1 peptide, a 16-mer peptide containing the entire CFR1 segment and part of the FR2 region of human V 8, showed both an immunoregulating and immunostimulating effect in murine AIDS. TCR V 8.1 peptide acts on T cells promoting interleukin-2 production and therefore enhancing a cellmediated immune response. It retarded development of cardiopathology due to coxsackievirus infection. Retrovirus infected mice treated with the peptide showed a longer life span than the ...
T cells play an important role in the pathogenesis of systemic lupus erythematosus (SLE). Clonal expansion of T cells correlating with disease activity has been observed in peripheral blood (PB) of SLE subjects. Recently, next-generation sequencing (NGS) of the T cell receptor (TCR) β loci has emerged as a sensitive way to measure the T cell repertoire. In this study, we utilized NGS to assess whether changes in T cell repertoire diversity in PB of SLE patients correlate with or predict changes in disease activity. Total RNA was isolated from the PB of 11 SLE patients. Each subject had three samples, collected at periods of clinical quiescence and at a flare. Twelve age-matched healthy controls (HC) were used for reference. NGS was used to profile the complementarity-determining region 3 (CDR3) of the rearranged TCR β loci. Relative to the HC, SLE patients (at quiescence) demonstrated a 2.2-fold reduction in repertoire diversity in a given PB volume (P |0.0002), a more uneven distribution of the
Development of the appropriate CD4+ T helper (TH) subset during an immune response is important for disease resolution. With the use of naive, ovalbumin-specific alpha beta T cell receptor transgenic T cell, it was found that heat-killed Listeria monocytogenes induced TH1 development in vitro through macrophage production of interleukin-12 (IL-12). Moreover, inhibition of macrophage production of IL-12 may explain the ability of IL-10 to suppress TH1 development. Murine immune responses to L. monocytogenes in vivo are of the appropriate TH1 phenotype. Therefore, this regulatory pathway may have evolved to enable innate immune cells, through interactions with microbial pathogens, to direct development of specific immunity toward the appropriate TH phenotype. ...