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The MHC encodes highly polymorphic cell surface glycoproteins which are recognized by T cells alone or in association with foreign antigens on the surface of target cells (for reviews see 1-3). Most cytotoxic T cells recognize antigen in the context of MHC class I molecules, while most helper T cells do so in the context of MHC class II molecules. In the BALB/c mouse, three restriction elements of class I, termed K, D, and L, and two of class II, called A and E, have been identified. In addition to the K, D, and L restriction elements, which are present on virtually all somatic cells, a growing number of tissue-specific MHC class I molecules (Qa-1, Qa-2, TL) have been characterized, the function of which is unknown.Mouse strains can be distinguished from one another by their particular sets of MHC alleles or haplotypes (4). Haplotypes are indicated by lower case letters, e.g., the BALB/c, C57BL/10, and AKR strains are representatives of the d, b, and k haplotypes. The MHC of the BALB/c mouse contains at least 33 class ! genes, 2 in the K region, 13 in the D and Qa regions, and 18 in the Tla region (5-7) (Fig. 1

The K, I and S regions of the mouse major histocompatibility complex (MHC) are composed of long tracts of DNA which differ in sequence divergence. A correlation exists between the location of an MHC gene in a variable or conserved chromosomal tract and the degree of polymorphism and diversity of the proteins encoded by its alleles. Variable tracts appear to be the result of mechanisms which mutate certain coding and non‐coding sequences to the same extent and selective pressures operating on the genes.

Over the past few years six gene clusters have been isolated from the major histocompatibility complex (MHC) of the BALB/c mouse encompassing a total of 1600 kb of DNA and 48 genes. The molecular distances between these gene clusters and the orientation of four of the six clusters on chromosome 17 is not known. Here we use pulse-field gradient gels and Southern blot hybridization to establish large-scale genomic restriction maps covering several hundreds of kb surrounding the three gene clusters located in the K, I, S, and D regions of the MHC. Comparison of the maps orients the complement gene clusters in the S region with the 21-OHB gene pointing towards the K end and the C2 gene pointing towards the D end of the MHC. The distances between the E, and 21-OHB genes is 430 kb and between the C2 and TNF-ca genes at least 420 kb.

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