Heterozygosity of H–2 loci in wild mice

Abstract

The major histocompatibility complex (MHC) is a cluster of genetic loci coding for cell surface molecules that seem to be the second most important element of the vertebrate immune system after immunoglobulins¹. The MHC loci can be divided into three classes. Class I loci code for molecules of about 44,000 molecular weight (MW) which seem to function as markers of self in T-lymphocyte-mediated cytotoxicity. Class II loci code for molecules consisting of two polypeptide chains, of MW 34,000 and 28,000 respectively, which are believed to regulate the immune response by controlling the behaviour of helper and suppressor T lymphocytes. Each molecule may carry several antigens—one ‘private’ (characteristic for the allele controlling this molecule) and several ‘public’ ones² (shared with molecules controlled by other alleles). Class III loci code for serum proteins. One of the most characteristic and remarkable properties of the MHC loci, in particular class I, is their genetic polymorphism, defined as the existence in a population of two or more alleles at appreciable frequencies^3–5. In H–2, the MHC of the mouse, individual alleles at class I K and D loci occur in the two populations that have been studied thus far with an average frequency of about 2% (ref. 5). We estimate, therefore, that these two populations contain some 100 alleles at each of the two loci. The polymorphism of class II locus A seems to be somewhat lower than that of the class I loci (average allelic frequency of 2–5%), while at the second class II locus (E) only five alleles have been identified⁵. The polymorphism implies that a high degree of heterozygosity should exist at the MHC loci in natural populations, and this has been found at the HLA loci, the human MHC (for review see ref. 6). We report here a similarly high frequency of heterozygosity in the mouse H–2 complex in a population of mice, in spite of a social structure that would tend to reduce heterozygosity.