Structure and function of murine class II major histocompatibility complex genes

The I region of the murine major histocompatibility complex (MHC) was first identified as a locus containing genes controlling specific immune responses (Ir genes). The same chromosomal segment was also found to include genes encoding highly polymorphic membrane antigens termed Ia (for I-region-associated) antigens. A combination of immunogenetic, serologic, and biochemical investigations demonstrated that the Ia antigens are heterodimeric cell surface glycoproteins, consisting of one heavy (α) and one light (β) chain in noncovalent association. Two isotypic forms of Ia are found in mice: I-A (A(β):A(α)) and I-E (E(β):E(α)). We now know that Ir genes are the structural genes for Ia molecules, and that the involvement of these Ia molecules in T-lymphocyte development and activation is responsible for Ir gene phenomena. Recently, the genes encoding the α and β chains of Ia were cloned and analyzed. This has permitted a detailed understanding of the complete protein sequence of allelic forms of each Ia subunit. DNA-mediated gene transfer has begun to be employed in correlating protein structure with function. The authors summarize here the date on the organization of class II genes and the relationship of allelic and isotypic variation to expression and immunologic activity.