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Front Immunol ; 15: 1342335, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38596688

RESUMO

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 insulin-producing pancreatic ß cells. Some HLA I alleles were shown to increase the risk of T1D (T1D-predisposing alleles), while some reduce this risk (T1D-protective 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.


Assuntos
Diabetes Mellitus Tipo 1 , Humanos , Linfócitos T CD8-Positivos , Antígenos de Histocompatibilidade Classe I , Peptídeos/metabolismo , Antígenos de Histocompatibilidade Classe II/metabolismo , Antígenos HLA/metabolismo , Antígenos de Histocompatibilidade/metabolismo
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