Self-antigens, benign autoimmunity and type 1 diabetes: a beta-cell and T-cell perspective - Inserm - Institut national de la santé et de la recherche médicale Access content directly
Journal Articles Current Opinion in Endocrinology, Diabetes and Obesity Year : 2022

Self-antigens, benign autoimmunity and type 1 diabetes: a beta-cell and T-cell perspective

Abstract

Purpose of review: 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. Recent 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. Summary: 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.
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Dates and versions

inserm-03834212 , version 1 (29-10-2022)

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Fatoumata Samassa, Roberto Mallone. Self-antigens, benign autoimmunity and type 1 diabetes: a beta-cell and T-cell perspective. Current Opinion in Endocrinology, Diabetes and Obesity, 2022, 29 (4), pp.370-378. ⟨10.1097/MED.0000000000000735⟩. ⟨inserm-03834212⟩
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