T-cell receptor beta-chain DNA polymorphism frequencies in healthy HLA-DR homozygotes.

In view of numerous recent reports of T-cell receptor (TCR) beta-chain/disease associations with HLA-associated diseases, we tested the possibilities that associations might exist directly between these two gene complexes at the level of the germline DNA. We determined frequencies of five TCR-beta DNA polymorphisms in 33 HLA-DR2/2 homozygotes, 29 HLA-DR3/3 homozygotes and 42 HLA-DR4/4 homozygotes. The control population (n = 74) was chosen without "bias toward" their HLA-DR genes. We selected DR2, DR3 and DR4 homozygotes because they have been the most frequently involved in HLA-DR associated diseases. Our results indicate that the recent reports in the literature of TCR-beta/disease associations can not be explained by a significantly different distribution of TCR-beta genes in HLA-DR2+, -DR3+, or -DR4+ subpopulations. Our results also suggest that if co-evolution between TCR-beta and MHC haplotypes does exist, the selective pressures in recent generations have not been strong enough to significantly alter the germline TCR-beta gene frequencies in HLA-DR2+, -DR3+, or -DR4+ subpopulations.