Doris Lambracht

Positive and negative MHC class I recognition by rat NK cells.

Summary: The prompt rejection of transplanted allogeneic lymphocytes by rat NK cells in non‐sensitized recipients (allogeneic lymphocyte cyto‐toxicity or ALC) is determined by MHC genes as well as by genes located in the NK complex. The same genetic control is found when NK alloreactivity is measured by an in vitro assay, and we have employed this assay to delineate the specificity of NK cells for the MHC. The MHC of the rat, RT1, contains class 1 genes situated on either side of the class Il/class III region. The majority of these class 1 genes are located in the RT1.C region and expressed class I products usually behave as non ‐classical (class Ib) molecules. They do not serve as restriction elements for the vast majority of conventional a/p T‐cells, in contrast to those class molecules encoded by one or more loci in the classical (doss la) region, RT1. A. However, NK cells appear to recognize the products of either class 1 region. Immunogenetic studies suggest that NK cells are inhibited by RT1.A molecules, whereas RT1.C region molecules may have a dual role in regulating NK cytolytic activity, i.e. they either inhibit or activate natural killing. Based on THESE premises, a model is proposed in which identification of a target as self or non‐self depends on different receptors for class 1 in single NK cells, interpreting coincident positive and negative signals from the various target class I molecules. The putative role of peptides presented by class I, the biological implications, and the evolution of the NK receptors and ether ligands are discussed.

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

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, 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 H2M4 are separated from other class I genes that differ

Rat RT1 orthologs of mouse H2-M class lb genes

Rats have at least 61 major histocompatibility complex (MHC) genes or fragments; in the mouse, 61 class I genes, pseudogenes, and gene fragments have been mapped and ordered. Despite their abundance and ubiquity, the biological relevance of the MHC class Ib genes is hotly debated and their function generally unknown. However, it is clear that some of them can bind and present peptide antigens. The H2-M3 gene encodes an MHC class Ib molecule, formerly called HMT, with unique specificity for N-formylated peptides; H2-M3 can therefore present prokaryotic as well as mitochondrial peptides to cytotoxic T lymphocytes (CTL), and it participates in the immune response to infection. We wanted to know whether this rare class Ib gene with an obvious function was conserved and expressed the in rat. 38 refs., 3 figs., 1 tab.

Sequence analysis of the promoter regions of the classical class I gene RT1.Al and two other class I genes of the rat MHC

Major histocompatibility complex (MHC) class I molecules present peptides to CD8+ T cells and thus play key role in immunosurveillance by T-cell-mediated mechanisms. Their expression depends on complex control mechanisms at two major levels: (1) regulation of transcription mediated through the promoter region and additional regulatory elements of the individual class I gene, and (2) availability of appropriate peptides in the endoplasmic reticulum required to stabilize the ternary complex consisting of class I {alpha} chain, {beta}{sub 2}-microglobulin ({beta}{sub 2}m), and peptide. In addition, differences in the ability of different {alpha} chains to bind {beta}{sub 2}m can influence the transport to and turnover within the cell membrane. We have now analyzed the promoter regions of class I genes of the LEW rat strain carrying the RT1{sup 1} haplotype. The analysis of three class I genes in this region has led to the identification of characteristic regulatory sequences. 20 refs., 2 figs.