Genetic control of immune response to the L-Glu, L-Lys, L-Phe terpolymer in man

We have demonstrated that human lymphocytes can respond to the synthetic polypeptide GLPhe upon in vitro challenge by the antigen similar to that of (H,G)-A-L, (T,G)-A-L, (Phe,G)-A-L, and GAT. Family studies further support our postulation that responses to these synthetic polymers are under dual gene control. Three families with intra-HLA-A/B recombinants provided mapping information for Ir-GLPhe genes. The response phenotype of the recombinant of family 21 localized the Ir-GLPhe genes toward the HLA-B of D regions, whereas recombinants of family 24 and 27 placed the Ir-GLPhe genes distal to HLA-B, toward the A region. This discrepant gene assignment can be explained by assuming that recombination occurred at different positions between HLA-A and HLA-B. In family 21, crossover occurred distal to the Ir genes, while for the other two, proximal to them. A second possibility is that as in the mouse the two complementing genes are situated in different regions of the human major histocompatibility complex (MHC) and all three of the cross-overs occurred between them with the putative Ir-GLPhe-1 located near the HLA-A region and Ir-GLPhe-2 on the HLA-D region or vice versa. A third possibility is that immune response required interaction between a complete HLA-D-like molecule encoded in the A region and another encoded elsewhere, perhaps in HLA-D.