Structure and expression of class I genes of the mouse major histocompatibility complex.

The major histocompatibility complex (MHC) plays an important role in the regulation of the immune response in vertebrates. The MHC in man (HLA) and the mouse (H-2) is the most thoroughly studied case of a complex of linked genes (see [I] for a review). The H-2 locus maps on the murine chromosome 17 (Fig. 1). Three different types of proteins are encoded by the H-2 region. The class I molecules regulate the killing of virus-infected cells. The virus antigen is recognized in association with class I proteins. This is known as MHC restriction of T-cell recognition [2]. The bestcharacterized class I molecules are the classical transpantation antigens found on virtually all cells, encoded by the H-2K, H-2D, and H-2L loci. Class I antigens are also encoded by the TL complex, adjacent to the classical H-2 loci. The Qa and Tla proteins are lymphoid differentiation antigens. Class I molecules are intrinsic membrane proteins with molecular weights (MW) of 40,000-45,000. They are associated with a smaller polypeptide, ß, microglobulin, MW 12,000, not encoded by chromosome 17. The class I1 genes were originally discovered as immune-response genes. They regulate the interaction of T-helper cells and B cells to induce antibody prod~ction [3]. The class I11 molecules encoded by the H-2 region are complement components. One of the most remarkable properties of the H-2 antigens is their genetic polymorphism. In fact, about 50 alleles at both the H-2K and H-2D loci have been detected. In this aspect, they differ sharply from almost all other genes. We are particularly interested in how the H-2 polymorphism is generated. We think it likely that the analysis of the class I genes by recombinant DNA techniques will provide some clues to the nature of the polymorphism.