Mapping of H2-M homolog and MOG genes in the rat MHC

Abstract

Class I genes of the rat major histocompatibility complex (MHC; RTI system) are encoded by two subregions, which are separated by regions coding for class II (RT1.B/D) and class III molecules. By convention, the RT1.A region is left of the class II region; it codes for one or very few classical class I molecules. The RT1. C/E region, located on the other side of the RT1 complex, contains a large number of class I genes (Jameson et al. 1992). The internal organization of this extended class I region has not been defined in detail. It is therefore of interest that genes similar to H2-M genes, which are the most distal group of class I genes in the mouse, have been demonstrated in the rat (Wang et al. 1991(Wang et al. , 1995. The rat genes similar to H2-M genes are now called RT1.M genes, and they are different from the previously defined oligomorphic class I gene RT1.M (Wonigeit and Hfinisch 1991), which has been renamed RT1. R (Gill et al. 1995). A homolog of the H2-M3 gene has been isolated, and the sequence of RT1.M3 cDNA is 88% identical to H2-M3 (Wang et al. 1995). RT1.M3 as well as homologs of H2-M2 and H2-M4 have been mapped with established recombinant haplotypes to the extended class I region on the RT1. C/E side of the class II/III region (Wang et al. 1995). We now report on a new recombinant haplotype, r38, derived from the parental strains LEW (RTIO and BN (RTIn), in which the rat homologs of H2-M2 and H2-M4 are separated from other class I genes that differ between haplotypes l and n. This recombinant defines a new class I subregion beyond RT1.C. It also permitted mapping of the rat gene that codes for the myelin/oligodendrocyte glycoprotein (MOG) to this region of the RT1 complex.Haplotype r38 was found in a detailed analysis of the LXB family of 12 recombinant inbred (RI) rat strains. The progenitor strains of this RI strain set are LEW and BN (Hedrich 1990). Accordingly, the individual strains are expected to possess either the RT1 l or the RT1 n haplotype. Of the 12 RI strains analyzed, eight had previously been shown to possess the RT1.A and RT1.B/D region of the RT1 l haplotype and four the RT1.A and RT1.B/D region of RTln. Serological typing for the polymorphic RTI.C region gene, RT1.C 1, present in the RT11 but not the RT1 n haplotype, gave concordant results, demonstrating that in all strains the RT1.C gene has been derived from the same parental haplotype as the RT1.A and RT1.B/D regions. This was confirmed by restriction fragment length polymorphism (RFLP) analysis with the rat class I probe pWW6.3 encoding the extracellular part of a rat class I molecule (Wurst 1988), which detects the RT1.A gene as well as multiple class I genes mapping to the RT1.C/E region (Fig. 1).Haplotype-specific patterns for the RT1.M genes, differentiating l and n, could be demonstrated with the H2-M2 probe after digestion of genomic DNA with Hin dII, and with the H2-M4 probe after digestion with Barn HI, Hin dIlI, or Pvu II (Table 1; Fig. 2). One RI strain, LXB17L, showed a deviant result: although typing as 1 in...

Physical Map and Expression Profile of Genes of the Telomeric Class I Gene Region of the Rat MHC

“…The H2-M4 orthologous gene RT1-M4 (21) maps to the third class I subregion, and the H2-M3 orthologous gene RT1-M3 (32) to the fourth subregion. Thus, the telomeric part of the whole contig corresponds to the mouse H2-M region, confirming and extending previously published genetic data (33).…”

“…2), as well as three copies of the Leh525 homologous marker. The RT1-M3c gene, together with the RT1-M2 gene (33), is localized on a contig that could not yet be linked to the main contig directly, but has been assigned to the RT1 region by fluorescence in situ hybridization (K. Helou and L. Walter, unpublished data). This finding is in accord with the identification of three H2-M3 homologous genes on a single clone of a rat yeast artificial chromosome (YAC) library (34).…”

Origin and evolution of the major histocompatibility complex class I region in eutherian mammals

“…These observations indicate that, while occurrences of MHCI genes outside the CMR are a common feature in the genomes of some eutherian groups, they occur haphazardly and species‐specifically in others (Figure ). Interestingly, in the elephant we found MHCI genes in an extended MHCI region (Figure ), a pattern previously reported only in rodents so far (Lambracht, Prokop, Hedrich, Lindahl, & Woniget, ; Yoshino et al, ). The similarity of MHCI genes in this extended region in two distantly related taxa is striking, and raises the question whether similar long‐term pathogenic burdens have resulted in the similar gene distributions.…”

Positive and negative MHC class I recognition by rat NK cells

“…Collectively these studies have provided evidence for complex modes of rat NK recognition of dass I molecules, where the critical variables may include not only the allelic specificities of class I molecules and the RTl regions from which they derive, but also the way in which the NK receptor repertoire matches the various RTI.A and C class I molecules present in the target. An analogy can be drawn here with the mouse H2 system where inhibitory effects of both H2-K and H2-D have been observed (55) and with human NK cells having inhibitory receptors for HLA-A, -B as well as -C alteles (6,56,57).…”