H-2-linked recessive Ir gene regulation of high antibody responsiveness to TNP hapten conjugated to autogenous albumin

The antibody response to the hapten 2,4,6-trinitrophenyl (TNP) conjugated to autogenous mouse serum albumin (MSA) is regulated by an Ir gene(s) located within the major histocompatibility complex (MHC). Both the qualitative and quantitative ability of congenic strains to produce TNP-specific antibodies are functions of the H-2 haplotype. Thus, mouse strains may be classified as high (H-2^d), intermediate (H-2^b, H-2^s), and low responders (H-2^a, H-2^k, H-2ⁿ, H-2^p, H-2^q). Antibody responses, as measured by antigen-binding capacities in modified Farr assays, were compared among strains carrying recombinant H-2 haplotypes and their hybrid progenies. Distinct high- and low-responder phenotypes were evident throughout the time course of both primary and secondary antibody responses. The gene locus controlling specific responsiveness to TNP-MSA, now designated Ir-6, was mapped within the I-B subregion of the H-2 complex. Recessive inheritance of high responsiveness was confirmed in hybrid progenies of three different low × high-responder crosses.