Processing of a multiple membrane spanning Epstein-Barr virus protein for CD8(+) T cell recognition reveals a proteasome-dependent, transporter associated with antigen processing-independent pathway. (1/9)

Epstein-Barr virus (EBV) latent membrane protein (LMP)2 is a multiple membrane spanning molecule which lacks ectodomains projecting into the lumen of the endoplasmic reticulum (ER). Human CD8(+) cytotoxic T lymphocytes (CTL)s recognize a number of epitopes within LMP2. Assays with epitope-specific CTLs in two different cell backgrounds lacking the transporter associated with antigen processing (TAP) consistently show that some, but not all, LMP2 epitopes are presented in a TAP-independent manner. However, unlike published examples of TAP-independent processing from endogenously expressed antigens, presentation of TAP-independent LMP2 epitopes was abrogated by inhibition of proteasomal activity. We found a clear correlation between hydrophobicity of the LMP2 epitope sequence and TAP independence, and experiments with vaccinia minigene constructs expressing cytosolic epitope peptides confirmed that these more hydrophobic peptides were selectively able to access the HLA class I pathway in TAP-negative cells. Furthermore, the TAP-independent phenotype of particular epitope sequences did not require membrane location of the source antigen since (i) TAP-independent LMP2 epitopes inserted into an EBV nuclear antigen and (ii) hydrophobic epitope sequences native to EBV nuclear antigens were both presented in TAP-negative cells. We infer that there is a proteasome-dependent, TAP-independent pathway of antigen presentation which hydrophobic epitopes can selectively access.  (+info)

The production of a new MAGE-3 peptide presented to cytolytic T lymphocytes by HLA-B40 requires the immunoproteasome. (2/9)

By stimulating human CD8(+) T lymphocytes with autologous dendritic cells infected with an adenovirus encoding MAGE-3, we obtained a cytotoxic T lymphocyte (CTL) clone that recognized a new MAGE-3 antigenic peptide, AELVHFLLL, which is presented by HLA-B40. This peptide is also encoded by MAGE-12. The CTL clone recognized MAGE-3--expressing tumor cells only when they were first treated with IFN-gamma. Since this treatment is known to induce the exchange of the three catalytic subunits of the proteasome to form the immunoproteasome, this result suggested that the processing of this MAGE-3 peptide required the immunoproteasome. Transfection experiments showed that the substitution of beta5i (LMP7) for beta5 is necessary and sufficient for producing the peptide, whereas a mutated form of beta5i (LMP7) lacking the catalytically active site was ineffective. Mass spectrometric analyses of in vitro digestions of a long precursor peptide with either proteasome type showed that the immunoproteasome produced the antigenic peptide more efficiently, whereas the standard proteasome more efficiently introduced cleavages destroying the antigenic peptide. This is the first example of a tumor-specific antigen exclusively presented by tumor cells expressing the immunoproteasome.  (+info)

Multiple Loci within the major histocompatibility complex confer risk of psoriasis. (3/9)

 (+info)

Case of Chlamydia-associated arthritis. (4/9)

We report a case of Chlamydia-associated arthritis in a 40-year-old man. The patient experienced four episodes of Chlamydia trachomatis urtethritis within a few years. During the present episode, polyarthritis developed a few days after Chlamydia trachomatis urethritis was noted. The patient was diagnosed as having Chlamydia-associated arthritis. Loxoprofen sodium and azithromycin were started. Antibiotics induced clinical improvement of urethritis, although arthritis persisted for 3 months. HLA-B27 was negative, but both HLA-B35 and B40 were positive. Thus, we speculate that positivity for both HLA-B35 and HLA-B40 contributed to the persistence of arthritis in this case. During the course, the levels of Th1, Th17 and regulatory T cells in the peripheral blood were increased on flowcytometry. Thus, we speculate that Th17 may play, at least in part, an important role of the pathogenesis in this case.  (+info)

Antimyosin antibodies in CNS-lupus. (5/9)

Anti-myosin antibodies (AMA) in the sera of patients with systemic lupus erythematosus (SLE) and healthy subjects were measured by ELISA. AMA were IgM dominant. The titers of AMA were significantly higher in active SLE than in inactive SLE and healthy subjects. AMA negative SLE patients have significantly lower serum IgM than that in AMA positive subjects. Frequency analysis of HLA antigens in SLE revealed that AMA positivity was associated with HLA-A11, AMA negativity with HLA-B40 and DR2, and those with central nervous system involvement (CNS-SLE) were associated with HLA-B40. The patients with CNS-SLE have low serum IgM, low titer of AMA and HLA-B40.  (+info)

Identification of 4 novel HLA-B*40:01 restricted minor histocompatibility antigens and their potential as targets for graft-versus-leukemia reactivity. (6/9)

 (+info)

HLA-B*40 allele plays a role in the development of acute leukemia in Mexican population: a case-control study. (7/9)

 (+info)

Chronic myelocytic leukaemia: HLA association and decreased erythrocyte C3b receptor expression. (8/9)

A series of 27 adult patients with chronic myelocytic leukaemia (CML) were examined for erythrocyte C3b receptor (EC3bR) expression. Twenty-five patients were successfully HLA typed and there was a positive association of CML with HLA-B40 (P less than 0.01). Only 10 (37%) of the patients were EC3bR positive (P less than 0.00001) compared to 223 healthy controls of whom 198 (89%) were EC3bR positive. The positivity of EC3bR and HLA-B40 occurred simultaneously in six patients (P less than 0.05). HLA-B40 positivity and EC3bR expression were correlated with the following variables: age at the time of CML diagnoses, duration of CML (until death or the end of follow-up period 1 July 1983), the stage of CML and simultaneous medication. EC3bR positive patients were significantly more often in remission (P less than 0.05) and also had shorter duration of the disease (P less than 0.005) then did EC3bR negative ones. No significant correlation existed between EC3bR status and the other parameters. The presence of HLA-B40 did not associate with any of the listed variables. These findings may indicate the loss of the receptor in the course of CML with increasing immaturity of cells released from bone marrow.  (+info)