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The discovery of linkage between the MHC and genetic control of the immune response
Author(s) -
McDevitt Hugh
Publication year - 2002
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1034/j.1600-065x.2002.18509.x
Subject(s) - congenic , biology , major histocompatibility complex , genetics , gene , genetic linkage , immune system , antigen , spleen , haplotype , immunology , allele
Summary: Immunization of rabbits, and inbred strains of mice with branched, multichain, synthetic polypeptides, such as (T, G) − A‐‐L and (H, G) − A‐‐L, revealed striking differences in the ability of different strains of mice to produce specific antibody. F1 and F1 × parental backcross mice revealed clear genetic control. Initial attempts to link this genetic control to known genetic markers were unsuccessful. The second approach, which attempted to transfer response from high or immediate responders into low responder recipients, initially encountered graft vs. host and host vs. graft reactions. The transfer of F1 spleen cells into the low responder parent demonstrated that ability to respond was a property of immunocompetent cells (spleen cells), not of the recipient's background genes. Mapping studies with recombinant H2 haplotype congenic strains, and a classic 4‐point mapping cross were concordant in placing the gene controlling this trait within the H2 complex, between the K and Ss loci. Subsequent studies mapped the genes for stimulation in the mixed lymphocyte culture reaction to the same position, suggesting cell surface expression. Production of antisera to ‘I‐region’ products defined ‘Ia’ antigens, the 2‐chain α/β MHC class II molecules.