CHAPTER 1 - Ir Genes: Antigen-Specific Genetic Regulation of the Immune Response

Abstract

Immune-response (Ir) genes are defined as genes that regulate the ability of an individual to produce an immune response, cellular or humoral, against a specific antigen. Thus, an Ir gene “defect” in the response to antigen X, which leads to absent or diminished response to this antigen, may have no effect on the response to thousands of other antigens. In the late 1960s, McDevitt's group was attempting to determine the critical cell type involved in Ir gene function by adoptively transferring various lymphoid cell populations. To avoid allogeneic effects of transplantation across an major histocompatibility complex (MHC) barrier, MHC-identical strains of mice were studied. In the course of this work, the group serendipitously made one of the most important discoveries about Ir genes, namely, their linkage to the MHC, in that case H-2 of the mouse. Shortly thereafter, it was found that the Ir gene for the poly-L-lysine (PLL) response in the guinea pig was linked to the MHC of that species as well, an indication of the generality of the finding.