The role of H-2 I region genes in regulation of the immune response.

The evidence of the past 10 years indicates that genes mapping in the I region of the mouse major histocompatibility complex (H-2) regulate a bewildering array of immunologic functions. A survey of H-2-linked specific immune response (Ir) genes shows that the phenotypic effect of these genes is to enable a particular inbred strain to discriminate and recognize remarkably precise chemical specificities, such as one or two amino acid interchanges in a polypeptide chain. The only I region gene products which have been identified to date are the Ia antigens. These include five readily detectable polypeptide chains (Aa, Ab, Ae, Ea, and Ii) and several other serologically distinct entities which are selectively expressed on functionally distinct T cell subsets (J1, J2?, J3? and C). The specificity of recognition of Ir genes would seem to require a larger number of I region gene products than can be generated even by combinatorial association of the four readily identifiable peptides (to give eight combinatorial associations) and the other serologically identified gene products. If the Ia antigens are to function as an antigen specific receptor system, separate from immunoglobulin molecules, there must be other, as yet undetected, I region gene products (e.g. Ia antigens). Alternatively, the known I region gene products could function by any one of several postulated mechanisms to generate an antigen specific T cell receptor system. The available evidence for the total number of I region gene products is reviewed, and the alternate possibilities are briefly discussed in this presentation.