Cytogenetic location: 6p21.3 Genomic coordinates (GRCh38): 6:30,500,001-36,600,000
Hsu et al. (1981) and Chan et al. (1984) described HLA-linked immune response (Ir) genes that control in vitro lymphoproliferative responses to challenge by certain synthetic polypeptide antigens (see 146950, 146960, 146810, 146820). Without prior in vivo immunization, human peripheral blood lymphocytes proliferate vigorously when cultured for 7 days in the presence of antigen. Presumably, this is a secondary response resulting from exposure of the subject to similar epitopes in nature. While responsiveness in most families segregated as a mendelian dominant trait, some mating between nonresponders produced responder offspring, suggesting that, as in the mouse, responsiveness requires 2 complementary loci. The complementary genes were in coupling when inheritance was 'dominant;' they were in repulsion when inheritance was 'recessive.' Chan et al. (1985) conducted further studies with the terpolymer composed of L-glutamic acid, L-lysine and L-phenylalanine. Again they concluded that 2 separate complementary loci in the MHC region are involved. Several models were proposed to account for seeming inconsistencies in the mapping data.
Chan, M. M., Bias, W. B., Hsu, S. H., Meyers, D. Genetic control of major histocompatibility complex-linked immune responses to synthetic polypeptides in man: (Phe,G)-A--L and GAT. Proc. Nat. Acad. Sci. 81: 3521-3525, 1984. [PubMed: 6427771] [Full Text: https://doi.org/10.1073/pnas.81.11.3521]
Chan, M. M., Bias, W. B., Hsu, S. H., Meyers, D. A. Genetic control of immune response to the L-glu, L-lys, L-phe terpolymer in man. Am. J. Hum. Genet. 37: 561-570, 1985. [PubMed: 3923830]
Hsu, S. H., Chan, M. M., Bias, W. B. Genetic control of major histocompatibility complex-linked immune responses to synthetic polypeptides in man. Proc. Nat. Acad. Sci. 78: 440-444, 1981. [PubMed: 6787587] [Full Text: https://doi.org/10.1073/pnas.78.1.440]