Mixed lymphocyte reactions for individuals with phenotypic identity for specific HLA-B,DR determinants: the role of linkage disequilibrium and of specific DR and other class II determinants.

Although many patients who might benefit from therapeutic bone marrow transplantation lack HLA identical sibling donors, results from many centers now indicate that transplants involving donors other than identical siblings have been successful in a substantial number of cases. Most of these cases were selected because cells from the patient and donor were compatible in mixed lymphocyte culture. We have previously shown that the prediction of mixed lymphocyte culture nonreactivity by HLA-B,DR matching is far more successful if the matched donors shared antigen combinations known to possess significant positive linkage disequilibrium. We now also show that cells from donors with unrelated haplotypes having the specific DR determinants DR1, DR2, and DR3 are more likely than cells from donors with other haplotypes to be mutually compatible in mixed lymphocyte culture. However, even cells from donors with haplotypes with the highest levels of positive linkage disequilibrium frequently show significant mutual stimulation which can, in selected family studies, be attributed to determinants like SB that map between HLA-D/DR and GLO.