{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T08:57:25Z","timestamp":1788857845328,"version":"build-2803163510"},"reference-count":66,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,3,25]],"date-time":"2024-03-25T00:00:00Z","timestamp":1711324800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Human leukocyte antigen (HLA) I molecules present antigenic peptides to activate CD8<jats:sup>+<\/jats:sup> T cells. Type 1 Diabetes (T1D) is an auto-immune disease caused by aberrant activation of the CD8<jats:sup>+<\/jats:sup> T cells that destroy insulin-producing pancreatic \u03b2 cells. Some <jats:italic>HLA I<\/jats:italic> alleles were shown to increase the risk of T1D (T1D-predisposing alleles), while some reduce this risk (T1D-protective alleles).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Here, we compared the T1D-predisposing and T1D-protective allotypes concerning peptide binding, maturation, localization and surface expression and correlated it with their sequences and energetic profiles using experimental and computational methods.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>T1D-predisposing allotypes had more peptide-bound forms and higher plasma membrane levels than T1D-protective allotypes. This was related to the fact that position 116 within the F pocket was more conserved and made more optimal contacts with the neighboring residues in T1D-predisposing allotypes than in protective allotypes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our work uncovers that specific polymorphisms in HLA I molecules potentially influence their susceptibility to T1D.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1342335","type":"journal-article","created":{"date-parts":[[2024,3,25]],"date-time":"2024-03-25T05:00:06Z","timestamp":1711342806000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Differences in F pocket impact on HLA I genetic associations with autoimmune diabetes"],"prefix":"10.3389","volume":"15","author":[{"given":"Xu","family":"Ren","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. W. 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