Evidence for extensive polymorphism of class I genes in the rat major histocompatibility complex (RT1).

Abstract

The major histocompatibility complex of the rat (RT1) has been poorly characterized with respect to the number, linkage, and polymorphism of class I genes. To estimate the number of class I RT1 genes and the relative extent of their polymorphism, we performed Southern blot analysis with liver DNA from rat strains expressing eight RT1 haplotypes. After digestion with EcoRI and BamHI, the DNA was separated on agarose gels, blotted onto nitrocellulose, and hybridized with mouse H-2 cDNA probes, pH-211 and pH-2iHa. Ten to 20 EcoRI and 13 to 20 BamHI bands hybridized with pH-2I11 and pH-211a; restriction fragment length patterns were observed to be highly polymorphic. The restriction fragments associated with different RT1 haplotypes differed by 17-70%; this range is similar to the differences observed between mouse H-2 haplotypes. The same restriction fragment pattern was observed in DNA from three different rat strains sharing the same RTI allele, confirming that the patterns were RTI-associated. Further, the RTI1 and RT11"' haplotypes, which differ at a single previously identified RT1-linked locus, were associated with EcoRI restriction pattern differences of 39-50%, confirming the supposition that RT1 class I genes identified by previous serological and T-cell-mediated assays have identified only a minority of the actual number of RT1-linked class I genes. In summary, the results reported in this communication demonstrate that the RT1 complex encompasses a large family of highly polymorphic class I genes similar to the H-2 and HL-A complexes of mouse and man.The major histocompatibility complexes (MHCs) of mammals include polymorphic class I and class II genes (1), whose products regulate various aspects of the immune response. Class I genes encode approximately 45,000-dalton cell surface glycoproteins; in the case of the mouse MHC, H-2, approximately 30 class I sequences have been identified by gene cloning experiments (2). Among these genes are the previously identified K, D, and L (3) genes expressed on the majority of somatic cells and the Qa (4) and Ti genes (5) differentially expressed on lymphocyte subpopulations. Class II genes encode Ia molecules composed of two glycoprotein subunits with molecular weights of approximately 32,000 and 28,000 (6); class II molecules are primarily expressed on B cells (7) and macrophages (8).The outstanding characteristic of class I and class II MHC genes of the two most extensively studied species, mouse and man (HL-A), is their high level of polymorphism. In the mouse, approximately 50 different alleles at both the H-2K and H-2D loci have been identified in inbred and wild mice (9, 10). The rat MHC, RTJ, has been suggested to be significantly less polymorphic than the H-2 and HL-A complexes. The RTI complex is composed of (i) class I genes, which are RTJ.A (H-2K and H-2D analogs) (11, 12), RTJ.C (Qa analog) (13) The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in acco...

Genomic DNA sequence and organization of a TL-like gene in the grc-G/C region of the rat

“…The A and E loci encode class I antigens and correspond by their location to the H-2K and H-2D loci in the mouse (Kunz et al 1982), and the C and G loci encode class I molecules that are similar to the mouse Q/TL antigens (Stock and Gunther 1982;Inomata et al 1987;. A principal difference in the genetic organization of H-2 and RT1 is that the level of serological polymorphism of the class I antigens is quite high in the mouse, whereas it is very low in the rat (Gill et al 1983), despite the fact that both species have approximately the same number (20-36) of class I hybridizing fragments in their genomic DNA (Steinmetz et al 1982;Palmer et al 1983;Weiss et al 1984;Gunther et al 1985;Cortese Hassett et al 1986). This observation may reflect the presence of a limited number of functional class I genes in the rat.…”

Multiple TL-like loci in the grc-G/C region of the rat

“…There is molecular evidence for a grc homolog in the mouse (Vincek et al 1990;Hunt et al 1993), and there is clinical evidence for a grc-like region in the human (Ho et al 1994;. The G/C region has many class I loci (Palmer et al 1983;GUnther et al 1985;Cortese Hassett et al 1986Jameson et al 1992;Rothermel et al 1993), some of which encode weakly immunogenic molecules that have a very restricted polymorphism. Genetic mapping studies (Kohoutova et al 1980;Stock and Gtinther 1982;Inomata et al 1986;Kunz et al 1989) place these loci 1.4-3 cM from RT1.A.…”

Effect of donor specific transfusion (DST) is restricted to the rat combination used and closely related with alloantibody in heart transplantation

“…Interestingly in a number of combinations DST was effective with graft in one direction but not in the other (Table 1). These phenomena may not be explained by simple differences of the rat major histocompatibility complex (MHC) between the donor and recipient (19).…”