Ir genes mapping to the H-2 region of the mouse MHC reflect the natural function of class I and II molecules as restriction elements for antigen-specific T-cell responses (Simpson and Gordon 1977, Benacerraf and Germain 1978, Berzofsky 1980, in press, Schwartz 1984). Cytotoxic T cells are generally class I-restricted, whereas helper T cells are class II-restricted. The restriction of suppressor cells is not clear, and in view of the evidence that a number of suppressor lines do not have rearranged T-cell receptor fl genes, their mechanism of antigen recognition remains unclear. The identity of the class I molecules which serve as restriction elements is clearly established from in vivo, in vitro, and transfection studies; namely, K, D, and L in their various alMic forms (some of which are "permissive" and others not) for antigens under this type of Ir gene control. K, D, and L molecules are expressed in almost all tissues. Other class I genes, of which there are many (more than 20 in the H-2 d and H-2 b haplotypes), do not appear to encode restriction elements. It is unclear how many of them are expressed and what their tissue distribution and function is.
The tissue distribution of class II MHC molecules is in general limited to cells of the reticuloendothelial system. Early immunochemical studies established that class II molecules are dimeric glycoproteins with a chains of approximately 33 kd and 13 chains of approximately 28 kd. Immunogenetic studies using intra-H-2 recombinant mouse strains implied the existence of multiple loci within the H-2I region, including I-A, I-B, I-J, l-E, and I-C (Sachs 1984). Subsequent immunochemical studies suggested that the I-A locus encoded the a and 13 chains of the A molecule, as well as the 13 chain of the E molecule, and that the I-E locus encoded the a chain of the E molecule (see Fig. 1