The MHC, disease and selection

Trowsdale, John

doi:10.1016/j.imlet.2011.01.002

Cited by 183 publications

(173 citation statements)

References 98 publications

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“…Like CD, most autoimmune diseases with HLA associations are associated with MHC class II alleles, including type 1 diabetes, multiple sclerosis, rheumatoid arthritis, and ulcerative colitis (48). Despite the association of these diseases with class II alleles rather than class I alleles, CD8 + effector T cells play an important role in the pathogenesis of these diseases.…”

Section: Discussionmentioning

confidence: 99%

Dietary gluten triggers concomitant activation of CD4 ⁺ and CD8 ⁺ αβ T cells and γδ T cells in celiac disease

Han

Newell

Glanville

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

181

146

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Celiac disease is an intestinal autoimmune disease driven by dietary gluten and gluten-specific CD4 + T-cell responses. In celiac patients on a gluten-free diet, exposure to gluten induces the appearance of gluten-specific CD4 + T cells with gut-homing potential in the peripheral blood. Here we show that gluten exposure also induces the appearance of activated, gut-homing CD8 + αβ and γδ T cells in the peripheral blood. Single-cell T-cell receptor sequence analysis indicates that both of these cell populations have highly focused Tcell receptor repertoires, indicating that their induction is antigendriven. These results reveal a previously unappreciated role of antigen in the induction of CD8 + αβ and γδ T cells in celiac disease and demonstrate a coordinated response by all three of the major types of T cells. More broadly, these responses may parallel adaptive immune responses to viral pathogens and other systemic autoimmune diseases.autoimmunity | mucosal immunity

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Section: Discussionmentioning

confidence: 99%

Dietary gluten triggers concomitant activation of CD4 ⁺ and CD8 ⁺ αβ T cells and γδ T cells in celiac disease

Han

Newell

Glanville

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

181

146

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“…13 The MHC region has been recognized as one of the most important genetic regions associated with many kinds of human disease, including autoimmune diseases, infections, and cancers. 14 Linkage disequilibrium (LD) is the non-random association of alleles at different loci, and the long-range LD blocks observed in MHC haplotypes 15 induce genetic fixity in this region. Our previous study revealed that the three common Japanese HLA haplotypes were highly conserved among unrelated individuals up to 8 Mb, and suggested that these haplotypes might contribute to the occurrence of acute GvHD in HLA-identical UR-HSCT.…”

Section: Introductionmentioning

confidence: 99%

High-risk HLA alleles for severe acute graft- versus -host disease and mortality in unrelated donor bone marrow transplantation

et al. 2016

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“…As a result, it has been the focus of extensive research in the context of mate choice for genetic benefits (Milinski 2006;Eizaguirre et al 2009; Trowsdale 2011).…”

Section: Introductionmentioning

confidence: 99%

Mate-guarding by male mandrills (Mandrillus sphinx) is associated with female MHC genotype

Setchell

Richards

Abbott

et al. 2016

BEHECO

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This is a pre-copyedited, author-produced PDF of an article accepted for publication in Behavioral Ecology following peer review. The version of record Setchell, J. M., Richards, S., Abbott, K. M. Knapp, L. A. (2016) Use policyThe full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-prot purposes provided that:• a full bibliographic reference is made to the original source • a link is made to the metadata record in DRO • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders.Please consult the full DRO policy for further details. LAY SUMMARYWe examined whether male mate-guarding in mandrills varies with female genotype. Males were less likely to mate-guard females with specific genotypes which may be disadvantageous to offspring, and more likely to mate-guard females with genes that were different to their own, which would result in genetically diverse offspring. ABSTRACTFemale choice for male major histocompatibility complex (MHC) genotype has been widely tested, but the relationship between male mating strategies and female MHC genotype has received far less attention. Moreover, few studies of MHC-associated mate choice test for the fitness effects underlying such choice. We examined mate-guarding by male mandrills, a species with intense male-male competition and female offspring care. We developed a statistical model based on 10 years of observations to describe how the probability a female is mate-guarded varies across her sexual cycle, among cycles and among females. We accounted for female rank, parity and maternal relatedness. We then tested whether the occurrence of mate-guarding is influenced by (i) MHC-dissimilarity, (ii) female MHCdiversity, and (iii) specific female MHC genotypes. Finally, we tested for associations between MHC variables and the ratio of neutrophils to lymphocytes in blood samples taken during routine captures. The best-fit models included either MHC-dissimilarity (males were more likely to mate-guard more dissimilar females, and there was some evidence of preference for intermediate MHC-dissimilarity), or a specific MHC supertype. Four of 11 supertypes investigated were influential and one had a strong negative influence on mateguarding. We found some evidence that the MHC genotype that attracted the least mateguarding was disadvantageous in terms of immune function. However, we did not find evidence that MHC-diversity was related to immune function. These results suggest that highly competitive males modify their mating behaviour based on female MHC genotype, and a possible fitness benefit to mate choice for specific genotypes.

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The MHC, disease and selection

Cited by 183 publications

References 98 publications

Dietary gluten triggers concomitant activation of CD4 ⁺ and CD8 ⁺ αβ T cells and γδ T cells in celiac disease

Dietary gluten triggers concomitant activation of CD4 ⁺ and CD8 ⁺ αβ T cells and γδ T cells in celiac disease

High-risk HLA alleles for severe acute graft- versus -host disease and mortality in unrelated donor bone marrow transplantation

Mate-guarding by male mandrills (Mandrillus sphinx) is associated with female MHC genotype

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The MHC, disease and selection

Cited by 183 publications

References 98 publications

Dietary gluten triggers concomitant activation of CD4 + and CD8 + αβ T cells and γδ T cells in celiac disease

Dietary gluten triggers concomitant activation of CD4 + and CD8 + αβ T cells and γδ T cells in celiac disease

High-risk HLA alleles for severe acute graft- versus -host disease and mortality in unrelated donor bone marrow transplantation

Mate-guarding by male mandrills (Mandrillus sphinx) is associated with female MHC genotype

Contact Info

Product

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About

Dietary gluten triggers concomitant activation of CD4 ⁺ and CD8 ⁺ αβ T cells and γδ T cells in celiac disease

Dietary gluten triggers concomitant activation of CD4 ⁺ and CD8 ⁺ αβ T cells and γδ T cells in celiac disease