Self-antigens, benign autoimmunity and type 1 diabetes: a beta-cell and T-cell perspective.
Journal
Current opinion in endocrinology, diabetes, and obesity
ISSN: 1752-2978
Titre abrégé: Curr Opin Endocrinol Diabetes Obes
Pays: England
ID NLM: 101308636
Informations de publication
Date de publication:
01 08 2022
01 08 2022
Historique:
pubmed:
2
7
2022
medline:
12
7
2022
entrez:
1
7
2022
Statut:
ppublish
Résumé
Recent work using immunopeptidomics and deconvolution of the antigenic reactivity of islet-infiltrating CD8+ T cells has expanded our knowledge about the autoimmune target epitopes of type 1 diabetes. The stem-like properties of autoimmune CD8+ T cells have also been described. We here propose a possible link between these findings. Weak major histocompatibility complex (MHC)-binding epitopes list among the major targets of human islet-infiltrating CD8+ T cells, likely resulting in low peptide-MHC presentation that delivers weak T-cell receptor (TCR) signals, especially in the face of low-affinity autoimmune TCRs. These weak TCR signals may favor the maintenance of the partially differentiated stem-like phenotype recently described for islet-reactive CD8+ T cells in the blood and pancreatic lymph nodes. These weak TCR signals may also be physiological, reflecting the need for self-peptide-MHC contacts to maintain homeostatic T-cell survival and proliferation. These features may underlie the universal state of benign autoimmunity that we recently described, which is characterized by islet-reactive, naïve-like CD8+ T cells circulating in all individuals. These observations provide novel challenges and opportunities to develop circulating T-cell biomarkers for autoimmune staging. Therapeutic halting of islet autoimmunity may require targeting of stem-like T cells to blunt their self-regeneration.
Identifiants
pubmed: 35777965
doi: 10.1097/MED.0000000000000735
pii: 01266029-202208000-00010
doi:
Substances chimiques
Autoantigens
0
Epitopes
0
Peptides
0
Receptors, Antigen, T-Cell
0
Types de publication
Journal Article
Review
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
370-378Informations de copyright
Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.
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