Polymorphism of the major histocompatibility locus in the wild Norway rat

Specific alloantisera against the eight Ag-B groups found in inbred strains of rats were capable of reacting with all wild Norway rats (Rattus norvegicus) tested. Absorption studies, antisera production, and progeny testing involving wild rats showed that the antigenic specificities detected in the wild rat population were similar, if not identical, to the Ag-B antigens present in inbred strains. Xenoantisera prepared in rabbits against rat erythrocyte antigens (Ag-C1 and/or C2) reacted with erythrocytes from each wild rat tested. Progeny testing involving these erythrocyte antigens was identical to that observed in inbred strains. The restricted genetic polymorphism of theAg-B alleles in the wild rat population suggests that the functional and evolutionary significance of the major histocompatibility complex in the rat may not depend upon a high degree of genetic variability.     

Linkage of severity of experimental allergic encephalomyelitis to the rat major histocompatibility locus

The incidence of EAE is determined by Ir-EAE, a gene linked to the rat MHC. EAE severity can be assessed by quantitative clinical and pathologic measures. Using these measures, one can say that disease severity in LBNF1 is approximately one-tenth that in Lewis. Analysis of LBNF2, LBC, BNBC, and parental Lewis strain reveals that severity is primarily a function of dose of Lewis MHC alleles. Non-MHC genes have a small but discernable effect.     

The complement components of the major histocompatibility locus

Polymorphism of complement components, recognized by differences in either their antigenic specificity or their electrophoretic mobility, together with studies of inherited deficiencies, has enabled many of their structural genes to be mapped. In humans, three genes (for C2, C4, and factor B) have been placed between HLA-D and HLA-B on chromosome 6 and in mice, C4 between H2-I and H2-D, chromosome 17. Structural studies show that these components have exceptional features. C2 and factor B which contain the proteolytic active site of the C3 and C5 convertases are of the classical and alternative pathway respectively and are similar in structure and function. Both are novel types of serine proteases. C4 (as C3) contains an intrachain thioester bond essential for hemolytic activity. Molecular genetic investigations are determining the relative positions of these genes, and their precise structure, and should clarify their relation to the inherited diseases which are associated with defects in this section of the human genome.     

Analysis of the rat major histocompatibility system by Southern blot hybridization

The organization of the rat major histocompatibility complex, RT1, was studied at the DNA level by Southern blot hybridization. Genomic DNA from eight different RT1 congenic rat strains was digested by various restriction enzymes and was hybridized under stringent conditions with probes of mouse class I and class II H-2 genes. Few cross-hybridizing DNA fragments, showing no polymorphism, were seen with class II A alpha and A beta probes. The class I probes allowed for the distinction of about 8 to 19 cross-hybridizing bands, which exhibited extensive polymorphism. With the use of five RT1 recombinants, about 20% of the DNA fragments could be mapped to the RT1.A region, which codes for the ubiquitously expressed class I antigens, and about 80% to the RT1.C region-determining class I-like antigens, which are different from RT1.A antigens with respect to tissue distribution, restriction function in immune responses, and allograft rejection. The number of class I genes present in the rat genome and the possible relationship of RT1.C to H-2Qa, Tla of the mouse are discussed.     

Autoimmune alleles at the major histocompatibility locus modify melanoma susceptibility

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Genetic definition of a further gene region and identification of at least three different histocompatibility genes in the rat major histocompatibility system

Two new recombinant haplotypes of the rat major histocompatibility system,RT1, have been detected in [LEW.1A (RT1 ^a ) ×LEW.1W (RT1 ^u )] × LEW 1N(RT1 ⁿ ) segregating hybrids. Recombinantr3 carries theRTL1. A region (determining classical transplantation antigens) and theRT1.B region (determining strong mixed lymphocyte reactivity and genetic control of antipolypeptide immune responsiveness) of the RT1^a parent, bur rejects RT1^a skin grafts. Recombinantr4 carries theA andB regions of the RT1^u parent, but rejects RT1^u skin grafts. The two histocompatibility genes detected are allelic to each other. The relevant locus, designated asH-C, maps to theB-region side of theRT1 system and appears to mark a thirdRT1 gene region,RT1.C. Availability of haplotypes r3 andr4 allowed the definition of a histocompatibility locus in theB region,H-B. The products ofH-C, H-B and of the previously describedH-A gene vary in antigenic strength.     

Gene order in the major histocompatibility complex of the rat

The loci in the major histocompatibility complex (MHC) of the rat which code for class I and class II antigens—RT1.A and RT1.B, respectively — have previously been separated by laboratory-derived recombinants and by observations in inbred and wild rats. Closely linked to the MHC is the growth and reproduction complex (Grc) which contains genes influencing body size (dw-3) and fertility (ft). These phenotypic markers were used in this study to orient the A and B loci of the MHC. Two recombinants were used for mapping. The BIL(R1) animal is a recombinant between the MHC and Grc, and it carries the haplotype RT1.A ^lB^lGrc⁺. The r10 animal is an intra-MHC recombinant, and it has the haplotype RT1.A ⁿB¹ Grc. These recombinants were characterized serologically, by mixed lymphocyte reactivity, by immune responsiveness to poly (Glu⁵²Lys³³Tyr¹⁵) and by the presence of the dw-3 gene. The data demonstrate that the gene order of the loci is: dw-3-RT1.B-RT1.A.     

Allelic diversity at the primate major histocompatibility complex DRB6 locus

The HLA-DRB6 gene (also called DRB/V1) has been found only in about 26% of human HLA haplotypes, i.e.; DR1, DRw10, and DR2-bearing ones (Corell et al. 1991). In contrast, exon-2 DRB6 sequences have been obtained from all tested primates: nine chimpanzees (Pan troglodytes), three gorillas (Gorilla gorilla) and three orangutans (Pongo pygmaeus); other apes which had already been sequenced (one gorilla and one chimpanzee) also had the DRB6 gene. Thus, all apes tested from three different species, some of them evolutionary separated by at least 14–16 million years, bear the DRB6 gene. In addition, more than one gene copy per haplotype has been found in one chimpanzee; this, together with the apparent loss of this gene in some of the human DR haplotypes, may indicate that the DR genome has undergone evolutionary changes more recently and more actively than class I or III genes. In addition, ten different and presumably allelic DRB6 exon-2 sequences have been obtained, and some of them coming from different species are more similar to each other than the one from the same species; this finding goes in favor of the trans-species theory of major histocompatibility complex polymorphism generation. Also, data are presented supporting that DRB6 may be one of the eldest genes of the DRB family, thus one of the first to diverge from the ancestral DRB gene.The contribution to this paper by A. Corell and P. Morales is equal, and the order of the authorship is arbitrary.     

A second locus and new alleles in the major histocompatibility complex class II (ELA-DQB) region in the horse

More than two nucleotide sequences of the second exon of the ELA-DQB region retrieved from a single animal and two different sequences isolated from horses homozygous in the major histocompatibility complex (MHC) region by descent indicated the existence of at least two ELA-DQB loci at the genomic level. New alleles detected by polymerase chain reaction single strand conformation polymorphism (SSCP) and defined by nucleotide sequencing of the second exon of the DQB gene(s) were described. Based on the level of nucleotide sharing, at least two groups of alleles were shown to exist. The newly defined alleles belonged preferentially to one of the groups. However, their specific locus assignment was not possible from the data collected. At least one of these alleles was shown to be transcribed. No frame-shift mutations were identified among the new alleles, although one pseudoallele containing a stop codon was identified at the genomic DNA level.     

Characterization of a class Ib gene of the rat major histocompatibility complex

The cDNA and a partial genomic sequence of a rat class I major histocompatibility (RT1) gene, 11/3R, is reported here. The sequence contains several unique amino acid residues at certain positions, mutations in exon 7 (which is not expressed), a mutation of the canonical exon 8 stop codon to a sense codon, and includes a long 3 unstranslated region (utr). The structure of exon 7 differs from that found in most rat class I genes and resembles exon 7 of most H-2K,D,L.Q genes. Parts of the 3 noncoding region are homologous to the RT1.A-4 and certain H-2 genes. Expression is detectable by northern blot analysis in mitogen-stimulated lymphocytes only, by polymerase chain reaction (PCR) in each tissue tested. After transfection into L cells 11/3R can be shown to be expressible at the cell surface. Probes derived from the 3 noncoding part crosshybridize with a number of restriction fragments which map to the RT1.C region, thus defining a subfamily of RT1.C region genes. Several members of this subfamily are deleted in the M1 RT1 mutant. The 11/3R gene presents typical features of a class Ib gene. Aspects of evolution and the potential of the gene are discussed.The nucleotide sequence data reported in this paper have been submitted to the GenBank molecule sequence data base and have been assigned the accession numbers X67503 ande X67504.     

Identification of a new locus in the Escherichia coli cotransduction gap that represents a new genetic component of the L-asparagine utilization system

A temperature-sensitive Escherichia coli mutant defective for the ability to utilize L-asparagine as a sole nitrogen source was isolated after N-methyl-N'-nitro-N-nitrosoguanidine mutagenesis. The mutation (asu) produces two distinct phenotypic effects. Mutant strains grow poorly at high temperature on minimal plates containing asparagine as the sole nitrogen source; this effect is greatly exacerbated by the presence of methionine. Mutant strains utilize L-asparagine as a nitrogen source three to four times more efficiently at permissive temperatures than the wild-type strains. The mutation maps at 32.4 min on the E. coli chromosome, within the E. coli cotransduction gap. Mutant strains produce normal amounts of thermo-stable L-asparaginase I activity. The mutation therefore affects a component of the asparagine utilization system other than the catabolism of asparagine within the cell; it probably affects asparagine uptake.     

The major histocompatibility complex of the rat,RT 1

Recombinational analysis has shown that the rat MHC,RT1 is divided into two regions:RT1.A, which codes for class I (transplantation) antigens, andRT1.B, which controls the humoral immune response and proliferative response to allogeneic cells as well as the expression of class II (Ia) antigens. Serological and sequence studies suggest that there might be more than one antigen-coding locus within theRT1.A region. Results obtained by sequential immunoprecipitation reveal that both regions code for at least two gene products. By implication, theRT1 complex must therefore harbor at least four loci;RT1.A andD coding for class I glycoproteins (45,000 daltons); andRT1.B andE coding for class II (Ia) glycoproteins (35,000 and 28,000 daltons).     

The major histocompatibility complex of the rat,RT1

The antigenic determinants expressed on RBC and lymphocytes and coded for by the MHC, RT1,of the MNR (RT1 ( m )) rat strain were compared to those of the BN.DA(RT1 ( a )), ALB (RT1 ( b )), and AUG (RT1 ( c )) strains by direct cytotoxicity and absorption analysis with RT1 typing sera, sera produced against MNR cells, and sera produced in MNR responders against cells carrying thea, b, andc haplotype determinants. The results indicate that MNR shares major class I (A) antigens with DA, and major class II (B) determinants with AUG, but that MNR differs from DA and AUG with respect to both classes of determinant. It appears, therefore, that the MNR haplotype does not represent a simple composite of the two other haplotypes,RT1 ( a ) andRT1 ( c ), as reported earlier.     

Linkage disequilibrium between two genetic loci of the major histocompatibility complex in rats

The major histocompatibility complex (MHC) in natural populations of rats is composed of genetic phenotypes that are similar, if not identical, to those seen in inbred laboratory strains. Examination of individual wild rats from a single location in the city of Pittsburgh, Pennsylvania, resulted in the identification of seven different RT1.A histocompatibility serotypes and three RT1.B mixed lymphocytes responses. In this population of animals there is a significant association (p < 0.005) between four RT1.A and RT1.B phenotypic pairs: RT1.A⁸B¹, RTl.A^kBⁿ, RTl.A^dB^a and RT1.A¹B^a. The observed values for linkage disequilibrium (0.211,0.076,0.070 and 0.085, respectively) are very high and are close to the maximum expected, given the individual allelic frequencies. Although the animals included in this study were obtained from one location, agreement with Hardy-Weinberg equilibrium is demonstrated for other loci in the same population. The demonstration of equilibrium suggests that significant inbreeding is not affecting this population of rats. Not enough is known about the allelic frequencies in surrounding rat populations to determine how important the effect of migration is on these disequilibrium values. The large linkage disequilibria may indicate that, in the rat, environmental selective forces are operating to ensure the nonrandom association of separate components of the MHC.