Structural relationships among the H-2 D-regions of murine MHC haplotypes

The number of genes encoding functional Ag-presenting molecules in the D region of the murine MHC differs among haplotypes. For example, the H-2^b D region contains a single 'D/L' gene, H-2D^b, whereas the d-haplotype encodes two, H-2D(d) and L(d). Using D/L specific oligonucleotide probes, we have found that, as with H-2(d), the q- and v-haplotypes contain two D/L genes, whereas the other haplotypes examined have one. Hybridization analysis using cloned probes that map between H-2D(d) and L(d) revealed similar structures in each of the three haplotypes (d, q, and v) which have 'duplicated' D regions. Two approaches were used to examine allelic relationships among the D/L genes. First, the 5' region of the H-2D^b was sequenced, and found to be more similar to H-2L(d) than to H-2D(d). Second, oligonucleotide probes that distinguish H-2L(d) from H-2D(d) revealed H-2L(d)-related genes in several haplotypes, including the duplicated haplotypes H-2(q) and H-2(v). Analogous probes specific for H-2D(d), however, did not detect similar sequences in the other haplotypes. We interpret these results to mean that the three duplicated D regions arose from a common duplication event, and share the five gene structure of the D region cluster defined in H-2(d). However, subsequent events have generated sequence divergence at the D-locus.