HLA-DP INCOMPATIBILITIES INDUCE SIGNIFICANT PROLIFERATION IN PRIMARY MIXED LYMPHOCYTE-CULTURES IN HLA-A, HLA-B, HLA-DR AND HLA-DQ COMPATIBLE INDIVIDUALS - IMPLICATIONS FOR ALLOGENEIC BONE-MARROW TRANSPLANTATION

The major part of the proliferative response in primary mixed lymphocyte cultures (MLC) is caused by HLA-DRBl incompatibilities. In DRBl-matched pairs the proliferation induced by HLA-DRB3, -DQ and -DP mismatches may be unmasked. In most previous studies the influence of HLA-DP incompatibilities in primary MLC has been investigated in homozygous typing cells representing only a few Dw specifities. We were interested in determining the stimulatory capacity of isolated HLA-DP mismatches, ascertained by RFLP analysis, in primary MLC in HLA-A, -B, -DR and -DQ compatible, unrelated heterozygous individuals of many different Dw specificities. Thirty-eight MLCs performed with cells from related pairs and 67 with cells from unrelated pairs were evaluated. All but nine of the MLCs were analyzed in both directions, giving a total of 201 investigated reactions. The relative responses (RR) in the three MLCs performed between DP incompatible, related pairs were all positive (RR greater-than-or-equal-to 8%). Eighty of 82 MLCs performed with cells from DP incompatible, unrelated individuals were positive, whereas 37 of 46 MLCs between DP compatible, unrelated pairs were negative (RR < 8%) (p < 10(-10). The magnitude of the RR was influenced by the number of DP mismatches. Thus, the mean RR was approximately twice as high in MLCs in which responder and stimulator cells differed by two DP antigens (mean RR 60.5%) compared with reactions with only one DP mismatch (mean RR 35.4%) (p < 10(-3)). RFLP-defined HLA-DP incompatibilities predict a positive primary MLC in HLA-A, -B, -DR and -DQ matched individuals with a high degree of accuracy (98%). We suggest that in the search for matched unrelated bone marrow donors HLA-DP typing might preferably precede and in many instances even replace MLC. This may well facilitate the search for compatible unrelated donors by reducing the number of MLCs.