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T H Hansen

Publications and source records attributed to T H Hansen.

120 records · Page 7Linked to original sources

Genetic control of the immune response to the H-2Dk private specificity, H-2.32. II. Genetic linkage analysis of a backcross generation.

B10.AKM mice (H-2M) when immunized with H-2k cells showed very low cytotoxic antibody responses to the H-2Dk private specificity H-2.32, whereas AKR.M and (AKR.M X B10.AKM)F1 mice that possess the same H-2m haplotype mounted reasonable anti-H-2.32 antibody responses. The genetic nature of the non-H-2 linked gene(s) controlling the anti-H-2.32 response was analyzed on the backcross progeny raised between (AKR.M X B10.AKM)F1 and B10.AKM mice. The anti-H-2.32 antibody response was found to be predominantly controlled by a single locus. This locus segregated independently of the Ig heavy chain locus, the Ly2 locus, and the Mls locus. Despite the observed difference in antibody production, no significant differences between AKR.M and B10.AKM mice were detected in induction of H-2Dk-specific killer T cells. Thus, the defect in the response of B10.AKM mice to H-2.32 can be detected at the level of B cell function and is controlled by a single non-H-2-linked genetic locus, but is not attributable to genes linked to the major immunoglobulin structural genes nor to the Mls locus.

Animals↗

Isolation and analysis of H-2 and Ia alloantigens from wild mouse strains.

Immunoprecipitation and SDS-PAGE analysis were used to examine H-2 and Ia antigens from mouse strains with wild-derived MHC haplotypes. Antisera raised against the wild-derived strains contained anti-H-2 and anti-Ia antibodies which precipitated antigen molecules readily distinguishable by a single assay procedure. The antibodies to wild strains were cross-reactive with standard laboratory haplotypes. Evidence supporting the similar genetic organization of wild and standard haplotypes was found, including isolation of separate H-2K and H-2D molecules from a wild-derived strain, and isolation of two separate Ia molecules from a wild-derived strain.

Animals↗

Mutation in a new H-2-associated histocompatibility gene closely linked to H-2D.

Sequential precipitations of soluble BALB/c antigen with antisera detecting private and public H-2 specificities indicated three distinct classes of molecules of 45,000 mol wt. However, only two of these classes of molecules were detectable in antigen from the loss mutant, BALB/c-H-2db. The class of molecules, detectable in the wild-type strain but missing in the mutant, does not bear private specificities but does react with an antiserum detecting H-2 public specificities. Absorption in mutant mice of the antiserum to public specificities, left antibodies specific for the antigen detectable in BALB/c but not BALB/c-H-2db. Genetic mapping studies using this specific antiserum indicated that the antigenic loss of this mutant is in a gene which maps in or close to the H-2D region, separable from the H-2K, S, G, Qa-2, and Tla regions.

Animals↗

Immunochemical evidence for an additional H-2 region closely linked to H-2D.

Anti-H-2 reagents have been tested on solubilized spleen cell preparations in combinations expected to be specific for D region products. Two different types of molecules were detected. One showed the expected reactivity with both antisera to private and antisera to public specificities. However, an additional molecule was detected which reacted only with antisera to public specificities. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis migration patterns indicated that both products have a similar molecular size of approximately 45,000 daltons. The data therefore present chemical evidence for the existence of a third H-2-associated gene product of 45,000 mol wt in addition to the classical H-2K and H-2D antigens.

Animals↗

Genetic control of the humoral response to an H-2 public specificity.

The humoral response of mice to an H-2 public specificity, termed H-2. '28' was found to be under genetic control. The genes determining this specificity were mapped to both the H-2K and H-2D regions, suggesting possible structural homologies between the products determined by these two regions. Genetic analyses indicated that a single non-H-2-linked gene regulates the anti-H-2. '28' response. In a backcross study, no linkage was detected between this putative H-2. '28' Ir gene and either the V H region or the Ly-2 locus to which the K-light chain locus is linked. Thus, a regulatory rather than a structural genetic locus seems a more likely basis for differences in response to this antigen. Our data further indicate that control of the humoral response to H-2. '28' is determinant specific since responses of the same backcross mice to other K and D alloantigens were not found to be subject to the same control.

Animals↗

Characterization of a constitutive variant of the murine serum protein allotype, Slp.

Properties of the Ss serum protein (putatively the murine homologue of the fourth component of complement) and its allotypic form, Slp, were studied in a wild-derived variant, Ssomega7. The Ssomega7 allele is unique in that it confers non-sex-limited expression of the Slp allotype. During examination of the H-2 haplotypes of two congenic lines which derived their Ssomega7 allele from a common origin, it was found that intra-H-2 recombination had occurred during the establishment of one of these lines. The sex-limited expression of Slp as determined by the Ssd allele was constrasted in several ways to the constitutive expression of Slp as determined by the Ssomega7 allele. Slp expression in mice carrying the Ssd allele was found to be subject to control by the testicular feminization mutant, Tfm, while in mice carrying Ssomega7 the Slp expression was independent of Tfm control. This implies that Slp is subject to a rather fundamental hormonal control mechanism in mice carrying Ssd and presumably all other Slp-positive Ss alleles, with the exception of Ssomega7. It is proposed that Ssomega7 may represent an "operator-constitutive" mutation of the Jacob-Monod type. Including the Ssomega7 allele, there are now at least seven distinguishable Ss variants. Each of these Ss alleles is characterized by a unique level of Ss and/or Slp antigenic expression. The sex-limitation difference and quantitative differences in Ss and Slp expression associated with the Ssomega7 allele were found to be codominant or intermedaite when Ssomega7 was in heterozygous combinations with other Ss alleles. This indicates a lack of trans effects and argues against genetic differences in regulatory proteins as the basis for these polymorphisms.

Alleles↗

Evidence for the involvement of the Ss protein of the mouse in the hemolytic complement system.

A significant within-strain correlation has been demonstrated between the levels of Ss and hemolytic complement (C) activity in two Ss-high strains. Mouse serum specifically depleted of Ss by absorption with F(ab')2 fragments of anti-Ss had negligible C activity. In control experiments, Ss-specific antigen-antibody complexes formed with F(ab')2 fragments did not fix rabbit C, and bovine serum albumin-specific antigen-antibody complexes formed with F(ab')2 fragments did not fix mouse C. Therefore the removal of C activity by anti-Ss [F(ab')2] was apparently not due to C fixation. These results suggest that the Ss protein is a necessary component of the C system.

Animals↗

Studies on recombination within the mouse H-2 gene complex. III. Further serological analyses of the H-2t haplotypes.

The five H-2t haplotypes are all intra-H-2 recombinants which have identical K and D regions, but differ in the central regions of the complex. Analyses of H-2, Ia and Ss-Slp types indicate that the crossover in H-2t1 took place between the K and I regions, in the H-2t2 between G and D, in H-2t3 and H-2t4 between the I-B and I-C subregions and in H-2t5 between I and S. The set of recombinants will be very valuable for studies of traits which map in the I and S regions.

Animals↗

Genetic control of the immune response to the H-2 associated Slp alloantigen in the mouse.

A survey of sixteen standard inbred and congenic resistant strains of mice reveals that the ability to mount an immune response to the Slp allotype is associated with the H-2 type of the recipient. Strains carrying the H-2f, H-2k, and H-2q haplotypes are able to produce specific antibody whereas strains of the H-2b haplotype are non-responders. Analysis of F1-hybrids and four informative intra-H-2-recombinants demonstrates that the ability to respond to the Slp allotype is controlled by a dominant gene associated with the K end of the H-2 complex.

Animals↗

Enumeration of H-2-gene products: failure to detect L molecules in the H-2b haplotype.

Sequential immunoprecipitation analyses have been performed in an attempt to demonstrate products of the H-2L locus of the H-2b haplotype. Antisera to the private H2Db specificity, H-2.2, were used to pretreat antigens preparations, and the supernatants were then examined with antisera to public H-2b specificities, including antisera cross-reactive with H-2Ld. In no case was a separate molecule detected. These findings are in marked contrast to the results of similar sequential precipitation analyses o;n H-2d and H-2q antigen preparations, in which L molecules are readily detected. Other sequential precipitation analyses were also performed on H-2k- and H-2s-antigen preparations and also failed to demonstrate distinct L molecules (data not included). We conclude that L molecules are either present in too low amount to be detected among the products of these other haplotypes, or that the H-2L gene represents a recent duplication and is present only in the H-2d and H-2q haplotypes among the inbred mouse strains surveyed.

Alleles↗