Two separate genes controlling stimulation in mixed lymphocyte reaction in man.

The genetic control of strong stimulation in the mixed lymphocyte culture reaction is determined by a separate gene (MLR-S) closely linked to the FOUR-locus of the HL-A chromosomal region. Three additional examples of siblings with recombination between FOUR-locus and MLR-S locus are presented which confirms the independent genetic control of mixed lymphocyte reaction from the control of HL-A antigens. The occurrence of two recombinant children in one family with four other children representing all possible HL-A haplotype-combinations, strongly supports the genetic mapping of the MLR-S determinants outside the HL-A chromosomal region. The experiments presented show that additional genes located within the HL-A region itself contribute with a weak stimulation of allogenic mixtures. These data are discussed in relation to the marginal stimulation of the mixed lymphocyte culture reaction which can be seen between unrelated individuals. It seems that a group of relatively histocompatible individuals can be defined by identity of the MLR-S locus but with differences on the weak MLC-determinants, and that this group for the purpose of clinical transplantation behaves as histocompatible individuals.