Transgenic mice expressing human HLA class II molecules provide a useful model for identifying HLA-restricted CD4+ epitopes. However, the influence of endogenous murine H-2-restricted T cell responses on HLA-restricted responses is not known. In the present study, we show that HLA-DR1 transgenic mice deficient for H-2 class II expression (HLA-DR1+/+/IAbeta0/0) exhibit an equivalent expression l...

PURPOSE NY-ESO-1 (ESO), a tumor-specific antigen of the cancer/testis group, is presently viewed as an important model antigen for the development of generic anticancer vaccines. The ESO(119-143) region is immunodominant following immunization with a recombinant ESO vaccine. In this study, we generated DRB1*0101/ESO(119-143) tetramers and used them to assess CD4 T-cell responses in vaccinated p...

Rheumatoid arthritis (RA) is found more often in subjects carrying the HLA-DR1 antigen and some subtypes of the HLA-DR4 antigen than in those without these antigens. Analysis of probes specific for HLA-DR4 has shown that amino acids encoding positions 69-74 (EQRRAA) of the beta chain indicates susceptibility to RA. A hexamer sequence of proteus haemolysin spanning residues 32-37 (ESRRAL) has be...

Forty-nine Israeli Jewish patients with rheumatoid arthritis (RA) were studied for their HLA A, B, C, DR antigen frequency. A significant increase in HLA Aw31 and HLA DR1 was observed (p less than 5.10(-5) and p less than 5.10(-3) respectively). 45% of Aw31 positive patients were sero-negative for rheumatoid factor, while most HLA DR1 positive individuals were seropositive. DR5 was found to be ...

Goodpasture's disease provides an opportunity to analyse molecular mechanisms that may underlie MHC class II associations with autoimmune disease because it is caused by autoimmunity to a defined antigen [the 230 amino acid NC1 domain of the alpha3 chain of type IV collagen (alpha3(IV)NC1)] and has strong HLA class II associations. We compared the alpha3(IV)NC1 peptide binding of class II molec...

Rheumatoid arthritis (RA) is an autoimmune disease that is strongly associated with the expression of several HLA-DR haplotypes, including DR1 (DRB1*0101). Although the antigen that initiates RA remains elusive, it has been shown that many patients have autoimmunity directed to type II collagen (CII). To test the hypothesis that HLA-DR1 is capable of mediating an immune response to CII, we have...

T cells from an HLA-DR11/DR12 responder were stimulated in mixed lymphocyte culture with cells carrying the DR1 antigen. After priming, T cells proliferated in response to both DR1-positive-stimulating cells and a peptide derived from a polymorphic region of the HLA-DR beta 1*0101 chain presented by responder's antigen-presenting cells (APC). The dominant epitope recognized by the primed T cell...

coronary  atherosclerotic  disease  is  one  of  the  most  endangering  health  disorder worldwide. this study was designed to investigate the correlation between hla-drβ1 alleles and circulating th1/th2 type cytokines in coronary atherosclerosis. by elisa, th1/th2 type cytokines were determined in serum samples of 31 subjects with unstable angina, 27 subjects with chronic stable angina and 24...

The susceptibility to develop seropositive rheumatoid arthritis (RA) has been linked to specific genomic polymorphisms within the HLA complex. Two different haplotypes have been associated with the disease, HLA-DR1 and HLA-DR4. To investigate the link between such phenotypic disease associations and potential immune mechanisms we used alloreactive and antigen-specific human T cell clones. Here ...

The superantigen staphylococcal enterotoxin A (SEA) binds to major histocompatibility complex (MHC) class II molecules at two sites on either side of the peptide groove. Two separate but cooperative interactions to the human class II molecule HLA-DR1 were detected. The first high affinity interaction to the DR1 beta chain is mediated by a zinc atom coordinated by H187, H225, and D227 in SEA and...