On the anomalous nature of the major histocompatibility complex in Syrian hamsters, Hm-1.
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Biomedical subjects
Publications and source records attributed to W R Duncan.
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Hamsters alloantisera and a monoclonal antibody originally generated against antigens controlled by the murine I-Ek subregion, which cross-reacts with hamster cell surface antigens, have been used to define two distinct Ia-like complexes in the Syrian hamster. These complexes have been named alpha 1:beta 1 and alpha 2:beta 2 and are detected by hamster alloantisera or monoclonal antibody 14-4-4, respectively. For the three strains studied, alpha 1:beta 1 appears to be polymorphic in both alpha and beta chains, while the alpha 2:beta 2 complex is nonpolymorphic, as revealed by 2-D PAGE analyses. A third nonpolymorphic glycoprotein that appears to be the hamster's equivalent of the murine invariant chain (Ii) is associated with both the alpha 1:beta 1 and alpha 2:beta 2 complexes. In addition, we report the first biochemical detection of polymorphism between the closely related CB and MHA Syrian hamster strains.
Immunochemical comparisons between hamster cell-surface p39/p29 alloantigens and putative MHC class I and II products indicate that p39/p29 alloantigens are probable class II products. Both p39/p29 alloantigens and class II homologues have varying expression in hamster lymphoid tissues and are absent from fibroblasts. In addition, analysis by nonequilibrium pH gradient electrophoresis demonstrates similar, although nonidentical, alloantigen and class II homologous charge profiles. This observation could reflect multiple class II subregions within the hamster MHC. These data therefore suggest an immunochemical description of the hamster MHC which is compatible with MHC models proposed for other mammalian species.
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Based primarily on studies in mice and man, the organization and gene-product structures of the mammalian major histocompatibility complex (MHC) are thought to be extensively conserved. However, attempts to generalize from the specific observations of other species to Syrian hamsters have not been completely successful. Previous studies in hamsters have suggested abnormal structure, expression, and/or function of the putative hamster MHC and its products. Characterization of hamster MHC gene-products is therefore of interest. This study concerns the identification and characterization of hamster cell-surface glycoproteins homologous to MHC products of man and mouse. Utilizing radioimmunoprecipitation and serologic techniques, these molecules have been characterized with regard to molecular weight, tissue distribution and immunochemical homology to human and murine class I and II MHC products. In addition, alloantisera raised between histoincompatible hamster strains have been similarly used to identify cell-surface alloantigens of this species. The alloantisera detect cell-surface hamster molecules with immunochemical properties and tissue distribution resembling MHC class II rather than class I products. Thus, in contrast to other species, hamsters appear not to express extensively polymorphic major transplantation antigens of the class I type. Some hamster alloantigens are apparently homologous of Ia determinants since their genes are linked to Hm-1. However, other alloantigens with similar molecular weights are seemingly encoded by genes unlinked to the hamster MHC. These data support the hypothesis that the hamster MHC contains genes which encode for molecular products similar to those described in man and mouse, but that the organization and/or expression of these genes may be atypical.
Cytotoxic alloantisera were raised between recently wild and classical inbred strains of Syrian hamsters. Antisera produced by immunizing the classical inbred strains with tissue from the partially inbred, recently wild hamsters detect several specificities shared between the classical and recently wild strains. Reciprocal mixed lymphocyte reactions between the two different groups of hamsters suggest that the new source of hamsters possesses several unique MLR phenotypes which may represent new Hm-1 haplotypes. Moreover, several recently wild strains express MLR phenotypes quite similar if not identical to the Hm-1a haplotype of the inbred strain, MHA. Genetic analyses of alloreactions between domestic inbred and recently wild strains suggest that a single locus or chromosomal region encodes the allodeterminants that induce strong MLR reactivity. Six unique MLR phenotypes have been defined which most likely represent haplotypes of the hamster MHC equivalent, Hm-1. Genetic linkage studies indicate that some alloantisera detect determinants encoded by loci closely linked to the MLR locus, and therefore define Hm-1 determinants. Moreover, other alloantisera recognize determinants encoded by a locus that is unlinked to Hm-1. These studies suggest that Syrian hamsters express a polymorphic MHC equivalent, Hm-1, which encodes determinants that induce both cell-mediated and humoral alloreactivity.
1. Two groups of ewes were fed on a cobalt-deficient diet throughout pregnancy; one group (group A) was given the diet from the beginning of pregnancy, whilst the other (group B) received the diet for 16 weeks before mating. The ewes in group A continued to receive the diet for 12 weeks post-partum. 2. The vitamin B12 content of serum was estimated on three occasions before parturition and, for group A ewes, at 12 weeks post partum. Urinary concentration of methylmalonic acid was also determined at intervals before the lambs were born. 3. Serum values for vitamin B12 indicated that the ewes in both groups were depleted of the vitamin, though those in group B were more severely affected, as was evidenced by the high incidence of perinatal mortality among the lambs born to these ewes. Perinatal mortality appeared to be associated with abnormally-high values for urinary concentration of methylmalonic acid. 4. Analysis of liver lipids and adipose tissue triacylglycerols of some of the vitamin B12 -deprived lambs which died before, or within 1 d of, birth showed that, compared with the corresponding tissues of control lambs, these lipids contained unusually high proportions of odd-numbered fatty acids (mostly 15:0, 17:0 and 19:0). This observation is discussed in relation to the likelihood that, in vitamin B12-deprived lambs, propionate becomes available as a primer unit for fatty acid synthesis when the metabolism of its carboxylation product, methylmalonic acid, is impaired due to partial lack of a vitamin B12-containing enzyme system.
Twelve hamster alloantisera, recently produced by mutual immunizations of domestic inbred strains and recently wild, partially inbred lines, identify two cell surface molecules, 29 and 39 kilodaltons, expressed by hamster lymphohematopoietic cells. Their expression on lymph node and spleen cells suggests that hamster T cells display cell surface class II homologues. None of the alloantisera identify putative hamster homologues of class I MHC molecules. The data are consistent with the hypothesis that hamsters possess a chromosomal region, tentatively designated Hm-1, that comprises genetic loci encoding alloantigens detectable by mixed lymphocyte reactivity and by serology, a region that resembles the I region of murine H-2.
The identity of the effector cell(s) mediating vaccinia virus-induced cytotoxic activity in Syrian hamsters undergoing acute virus infection has been investigated. Two different approaches have been utilized in this regard. Although T cells do not mediate vaccinia virus-induced cytotoxic activity directly, studies employing adult thymectomized, x-irradiated, bone-marrow-reconstituted hamsters lacking discernible T cell reactivity demonstrated that the presence of an intact thymus and/or functional T cells were required for the in vivo development of a significant portion of vaccinia virus-induced cytotoxic activity. In addition, incorporation of aggregated gamma-globulins as well as anti-immunoglobulin reagents into the in vitro 51Cr release assay inhibited a significant proportion of the cytotoxic activity mediated by spleen cells obtained from acutely infected hamsters possessing an intact thymus. Both approaches have yielded information consistent with the idea that a sizable portion of vaccinia virus-induced cytotoxic activity in the Syrian hamster is effected by K cells mediating antibody-dependent cell-mediated cytotoxicity (ADCC). The significance of this observation is discussed with regard to hamster viral immunity in general.
Thirteen new B10.W congenic lines carrying wild-derived H-2 haplotypes on the genetic background of the C57BL/10Sn (=B10) strain, were analysed serologically for antigens encoded by the H-2K and H-2D loci. The analyses resulted in the description of 12 new private or low-frequency public H-2 antigens (designated H-2.127 through H-2.130, and H-2.133 through H-2.142) and six new H-2 haplotypes (designated H-2w21 through H-2w27). Six inbred, private or low-frequency public H-2 antigens were also found in the B10.W lines: H-2.17 in B10.CHA2, H-2.19 in B10.GAA37. H-2.21 in B10.DRB62 and B10.WOA105, H-2.25 in B10.STA62, H-2.31 in B10. KPA44 and B10.KEA5, and H-2.32 in B10.BUA16 and B10.BUA19. Virtually all these antigens occur in combinations with other class I antigens not represented among the available inbred strains, and thus constitute natural H-2 recombinants. Lines B10.LIB55, B10.STA10, and B10.STA12 appear to share the same K and D alleles; serologically indistinguishable are also lines B10.BUA16 and B10.BUA19, and B10.WOA105, B10.SNA57, and B10.DRB62.
A large number of genetically defined, isogenic strains of domestic Syrian hamsters (BIO) have been studied for their immunogenetic relationship to the inbred hamster strains MHA and CB, and to a partially inbred, recently wild strain, MIT. The results indicate that all BIO strains are histoincompatible with the inbred and recently wild strains maintained in our colony. They reject exchanged skin allografts, their lymphocytes participate in vigorous mutual mixed lymphocyte reactions. Moreover, transplantation alloantigens have been identified by serological testing with antisera recently developed by immunizing inbred hamsters with tissue from recently wild animals and vice versa. However, the incompatibility is strongest with the CB and MIT strains. Individual hamsters from many of the BIO strains accept MHA skin grafts indefinitely, fail to respond to MHA cells in mixed lymphocyte reactions, and type serologically as identical to MHA. We concluded that there must have been very little alloantigenic variation present among the three littermate hamsters caught in 1930 from which the local inbred and BIO lines are derived. Moreover, after 40 years there has been little, if any, mutational change in this restricted gene pool, at least as it can be expressed in histocompatibility assays. These findings address the issue of the extent of alloantigenic diversity among Syrian hamsters.
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Branched-chain fatty acids of perinephric triacylglycerols of semi-feral fallow deer (Dama dama dama) were analyzed by high resolution gas chromatography-mass spectrometry. Of the total fatty acids, 15.50% were Branched-chain components including 8.96% iso acids, mostly 14-methylpentacanoic acid, 2.85% anteiso acids and 1.73% of other monomethyl-substituted acids; dimethyl-branched acids with an iso structure (1.05%) and with an anteiso structure (0.18%) were also present. Whereas the predominant iso acids and methyl-substituted iso acids had chain lengths of 13 and 15 carbon atoms, the anteiso acids and methyl-substituted anteiso acids had chain lengths of 14 and 16 carbon atoms. Methyl substitution occurred on the even numbered carbon atoms relative to the carboxyl group. The general composition is also given of the fatty acids comprising the triacylglycerols of subcutaneous (rump area) and perinephric adipose tissue.
A concentrate of branched chain fatty acids (as methyl esters) was prepared from the triacylglycerols of subcutaneous adipose tissue lipids of lambs receiving a carbohydrate-rich (cereal diet). This was accomplished by procedures which allowed the removal of unsaturated components by peroxidation and straight chain saturated components by urea-adduct formation. The concentrate was analyzed by high resolution gas chromatography in combination with mass spectrometry and was shown to consist of a complex mixture of saturated methyl-substituted fatty acids. Methyl substitution occurred on even-numbered carbon atoms (relative to the carboxyl group) and the chain lengths of the acids ranged from 10 to 18 carbon atoms. Acids with one methyl substituent in the fatty acyl chain were most abundant; di-, tri- and tetramethyl-substituted acids were also present. The biosynthesis of these methyl-substituted acids is discussed briefly.
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1. The fatty acids of the triacylglycerols of subcutaneous adipose tissue of cattle, sheep, goats and red deer (Cervus elaphus) which consumed either herbage or a barley-rich diet were analysed for their content of branched-chain components. 2. Whereas the consumption of the barley-rich diet by sheep and goats was associated with the occurrence of relatively high proportions of branched-chain fatty acids, it was not in cattle and red deer.