Variations in the T-cell repertoire against HLA antigens in humans.

Allospecific anti-HLA class I antigen cytotoxic T-lymphocyte precursor frequencies (CTLpf) have been estimated in peripheral blood of healthy blood donors with responder stimulator combinations mismatched for one HLA-A,B antigen. The CTLpf ranged from 1 in 400 to 1 in 10,000, with most frequent values of 1 in 600 to 4000. The following observations were made: (1) CTLpf against the same HLA antigen vary among different responders; (2) CTLpf of one responder against various HLA antigens may be different; (3) "narrow" responders produce cytotoxic T lymphocytes that recognize only the private (stimulator) alloantigen, while "broad" responders produce mainly broadly cross-reactive cytotoxic T lymphocytes with public specificity. Split-well analysis shows that very few cytotoxic T lymphocytes of "broad" responders recognize the private alloantigen only. These individual variations are not dependent on the HLA phenotype, because they also occurred in unrelated HLA-identical responders stimulated against the same mismatched stimulator cells.