The major histocompatibility complex of tassel-eared squirrels

Wettstein, Peter J.; States, Jack S.

doi:10.1007/bf00364527

Cited by 10 publications

(3 citation statements)

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“…Furthermore, determinant selection can also be influenced by the efficiency of antigen processing [34]. Nevertheless, the mechanism of immunodominance in responses to MiHA cannot be directly extrapolated from these studies because it cannot be attributed simply to determinant selection or Tcell repertoire [8,12,131. Since dominated MiHA are well expressed on APC, and the responding T cell repertoire contains specific CTL for both the dominant and the dominated MiHA, the question that arises is why are Tcell responses restricted to dominant MiHA?…”

Section: Introductionmentioning

confidence: 99%

On the mechanisms of immunodominance in cytotoxic T lymphocyte responses to minor histocompatibility antigens

et al. 1997

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Although there are numerous minor histocompatibility antigens (MiHA), T cell responses leading to graft-versus-host (GVH) and graft-versus-tumor effects involve only a small number of immunodominant MiHA. The goal of the present study was to analyze at the cellular and molecular levels the mechanisms responsible for MiHA immunodominance. Cytotoxic T lymphocytes (CTL) generated in eight combinations of H2b strains of mice were tested against syngeneic targets sensitized with HPLC-fractionated peptides eluted from immunizing cells. The number of dominant MiHA was found to range from as little as two up to ten depending on the strain combination used. The nature of dominant MiHA was influenced by both the antigen profile of the antigen-presenting cells (APC) and the repertoire of responding CTL. When C57BL/6 dominant MiHA (B6dom) and H-Y were presented on separate APC, they showed similar immunogenicity. In contrast, when they were presented on the same APC, B6dom MiHA totally dominated H-Y. B6dom MiHA did not suppress anti-H-Y responses by acting as T cell receptor antagonists for anti-H-Y CTL, nor were anti-B6dom CTL precursors more abundant than anti-H-Y CTL precursors. Dominance resulted from competition for the APC surface between anti-B6dom and anti-H-Y CTL; the crucial difference between the dominant and the dominated MiHA appears to depend on the differential avidity of their respective CTL for APC. The only B6dom epitope thus far identified is the nonapeptide AAPDNRETF presented by H2-D(b). We found that compared with other known D(b)-binding peptides, AAPDNRETF is expressed at very high levels on the cell surface, binds to the D(b) molecule with very high affinity, and dissociates very slowly from its presenting class I molecule. These data indicate that one cannot predict which MiHA will be dominant or dominated based simply on their respective immunogenicity when presented on separate APC. Indeed, the avidity of T cell/APC interactions appears to determine which antigen(s) will trigger T cell responses when numerous epitopes are presented by the same APC.

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Section: Introductionmentioning

confidence: 99%

On the mechanisms of immunodominance in cytotoxic T lymphocyte responses to minor histocompatibility antigens

et al. 1997

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“…We used DNA samples originally collected as part of previous genetic studies of the Abert’s squirrel species complex [ 21 , 22 , 51 – 53 ], and also obtained 14 additional tissue samples from the Museum of Southwestern Biology, and one S. griseus tissue sample from The Museum of Vertebrate Zoology at Berkeley for use as an outgroup. We follow subspecies designations as proposed by Hoffmeister & Diersing [ 20 ] to describe sample populations.…”

Section: Methodsmentioning

confidence: 99%

“…1 , and detailed location information is given in Additional file 2 . Genomic DNA from samples used in earlier studies were prepared as previously described [ 21 , 22 , 51 – 53 ]. Museum samples (spleen or liver) were preserved in ethanol and DNA was extracted using the Qiagen DNeasy Blood and Tissue kit following manufacturer’s protocols.…”

Section: Methodsmentioning

confidence: 99%

Genome-wide markers reveal a complex evolutionary history involving divergence and introgression in the Abert’s squirrel (Sciurus aberti) species group

et al. 2018

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BackgroundGenetic introgression between divergent lineages is now considered more common than previously appreciated, with potentially important consequences for adaptation and speciation. Introgression is often asymmetric between populations and patterns can vary for different types of loci (nuclear vs. organellar), complicating phylogeographic reconstruction. The taxonomy of the ecologically specialized Abert’s squirrel species group has been controversial, and previous studies based on mitochondrial data have not fully resolved the evolutionary relationships among populations. Moreover, while these studies identified potential areas of secondary contact between divergent lineages, the possibility for introgression has not been tested.ResultsWe used RAD-seq to unravel the complex evolutionary history of the Abert’s squirrel species group. Although some of our findings reinforce inferences based on mitochondrial data, we also find significant areas of discordance. Discordant signals generally arise from previously undetected introgression between divergent populations that differentially affected variation at mitochondrial and nuclear loci. Most notably, our results support earlier claims (disputed by mitochondrial data) that S. aberti kaibabensis, found only on the north rim of the Grand Canyon, is highly divergent from other populations. However, we also detected introgression of S. aberti kaibabensis DNA into other S. aberti populations, which likely accounts for the previously inferred close genetic relationship between this population and those south of the Grand Canyon.ConclusionsOverall, the evolutionary history of Abert’s squirrels appears to be shaped largely by divergence during periods of habitat isolation. However, we also found evidence for interbreeding during periods of secondary contact resulting in introgression, with variable effects on mitochondrial and nuclear markers. Our results support the emerging view that populations often diversify under scenarios involving both divergence in isolation and gene flow during secondary contact, and highlight the value of genome-wide datasets for resolving such complex evolutionary histories.Electronic supplementary materialThe online version of this article (10.1186/s12862-018-1248-4) contains supplementary material, which is available to authorized users.

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T-cell receptor genes in tassel-eared squirrels (Sciurus aberti)

et al. 1990

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The role of environmental factors in the evolution and maintenance of diversity of antigen receptor gene families which participate in the immune response in mammals is inadequately understood. In order to elucidate the impact of these factors, we have undertaken the analysis of these gene families in the tassel-eared squirrel (Sciurus aberti) which has been separated into discrete subspecies by geographic barriers and whose food resources can be quantitated for estimating environmental quality. In this communication we describe the initial analysis of the complexity and polymorphism of sequences related to T-cell receptor (Tcr) alpha and beta chain genes in two subspecies, Sciurus aberti aberti (Abert) and Sciurus aberti kaibabensis (Kaibab) which have identical habitats and are separated by the Grand Canyon in Arizona, USA. Genomic blot analysis of 60 Abert and 62 Kaibab individuals collected over a 3-year period was performed with mouse Tcrb and Tcra cDNA probes. Sequences homologous to Tcrb-C, Tcrb-J1, and Tcrb-J2 genes were observed in all individuals from both subspecies; although Tcrb-J1 fragments were monomorphic. Tcrb-C and Tcrb-J2 fragments were polymorphic with both species- and subspecies-specific sequences. A single, monomorphic Tcra-C fragment was observed in addition to multiple Tcra-V fragments homologous to the mouse Tcra-V1 subfamily. Abert samples exhibited greater numbers of Tcra-V1 fragments as well as greater polymorphism than Kaibab samples. Heterozygosity estimates of Tcrb-C and Tcra-V1 sequences were determined for annually collected samples and compared with the yearly estimates of availability of hypogeous fungi, one of the major diet items of tassel-eared squirrels. In the Kaibab annual collections, Tcra-V1 heterozygosity declined with the decline in food resource, whereas heterozygosity of Tcrb-C sequences was inversely related to food resource. Similarly, a reduction in food resource for Abert squirrels in 1985 coincided with an increase in Tcrb-C heterozygosity in the same year. These results suggest that the diversity of gene families which participate in the immune response in mammals may be affected by environmental factors.

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The major histocompatibility complex of tassel-eared squirrels

Cited by 10 publications

References 43 publications

On the mechanisms of immunodominance in cytotoxic T lymphocyte responses to minor histocompatibility antigens

On the mechanisms of immunodominance in cytotoxic T lymphocyte responses to minor histocompatibility antigens

Genome-wide markers reveal a complex evolutionary history involving divergence and introgression in the Abert’s squirrel (Sciurus aberti) species group

T-cell receptor genes in tassel-eared squirrels (Sciurus aberti)

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