Frequency analysis of HLA-specific cytotoxic T lymphocyte precursors in humans

Frequencies of HLA class 1-specific cytotoxic T lymphocyte precursors (CTLp) from 33 responders were determined in 115 responder/stimulator combinations. In each combination there was a single HLA-A or HLA-B antigen mismatch. A wide range of CTLp frequency (CTLpf) values was found for most A and B locus antigens. Some A locus antigens appeared less immunogenic than other A locus antigens. The effect of additional C locus differences was negligible. The relationship between responder and stimulator HLA antigens is of minor importance because HLA-specific CTLpf against crossreactive (CREG) and subtype antigens were not significantly lower than CTLpf against non-CREG antigens. The CTLpf did not correlate with Bw4 or Bw6 mismatches. The existence of a broad range of values for HLA class I-specific CTLpf is of general interest. We have arbitrarily subdivided the CTLpf values into high, medium, low, and very low. In about 20% of the combinations the HLA-specific CTLpf were low or not even detectable in our assay. In contrast, HLA-specific CTLpf in combinations with multiple HLA antigen differences were regularly high. Our results confirm the high values of allospecific CTLpf in general but simultaneously point to unexpected variations. Frequency analysis of HLA-specific CTLp may be considered a new parameter in clinical transplantation for the selection of appropriate donor/recipient pairs.