Homozygous expression of MHC-II alleles that confer susceptibility to type 1 diabetes limits the efficiency of thymic negative selection and allows for CXCR6+ pathogenic clones to orchestrate the disease process. Expression of a second MHC-II allele decreases β-islet CD4+ T cell affinity, and limits CD8 cross-priming and diabetes risk without presenting the cognate MHC-II islet self-antigen.
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References
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This is a summary of: Stadinski, B. D. et al. I-Ag7 β56/57 polymorphisms regulate non-cognate negative selection to CD4+ T cell orchestrators of type 1 diabetes. Nat. Immunol. https://doi.org/10.1038/s41590-023-01441-0 (2023).
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MHC-II heterozygosity limits type 1 diabetes susceptibility through negative selection. Nat Immunol 24, 573–574 (2023). https://doi.org/10.1038/s41590-023-01446-9
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DOI: https://doi.org/10.1038/s41590-023-01446-9
