| Autor: |
Ren, Xu, Amarajeewa, A. W. Peshala, Jayasinghe, M. D. Tharushika, Garstka, Malgorzata A. |
| Předmět: |
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| Zdroj: |
Frontiers in Immunology; 2024, p1-17, 17p |
| Abstrakt: |
Introduction: Human leukocyte antigen (HLA) I molecules present antigenic peptides to activate CD8+ T cells. Type 1 Diabetes (T1D) is an auto-immune disease caused by aberrant activation of the CD8+ T cells that destroy insulinproducing pancreatic b cells. Some HLA I alleles were shown to increase the risk of T1D (T1D-predisposing alleles), while some reduce this risk (T1Dprotective alleles). Methods: 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. Results: 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. Conclusion: Our work uncovers that specific polymorphisms in HLA I molecules potentially influence their susceptibility to T1D. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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