Position of a locus determining mixed lymphocyte reaction distinct from the known HL‐A loci

Abstract Bilateral and unilateral mixed lymphocyte culture (MLC) tests were performed in five families, each containing one sibling in which recombination between the genes determining the antigens of the LA and Four segregant series of IIL‐A had occurred. The results confirm the very weak or non‐stimulatory effect of antigens of the LA segregant series, bringing to seven the total number of alleles for which this has been shown so far. Further anomalies in one of the families, however, indicate that the antigens of the Four segregant series are not fully responsible for MLC activation either. Of a group of three HL‐A identical siblings, one proved to be MLC‐positive with the other two, but MLC‐negative with another group of two HL‐A identical siblings, which group displayed a one‐allelic difference for HL‐A with the former group. Furthermore, the child showing this unexpected MLC reaction pattern proved also to be MLC‐negative with the earlier mentioned sibling who had the serologically demonstrable recombination between the LA and Four series, notwithstanding a difference for three HL‐A antigens. These findings are interpreted as strong evidence for the occurrence of a recombination between the HL‐A loci and a MLC determining locus, which can thus be localize outside the previously recognized HL‐A region close to the Four locus. The relationships between HL‐A, MLC, skin graft rejection and organ transplantation are reexamined in the light of this concept.