Table 1.

Characteristics and roles of different types of islet autoantigen-specific T cells.

Autoantigen-specific T cells	Identify epitopes/proteins	How to play a pathogenic role	Role in T1DM	Possible therapeutic implications	References
Preproinsulin-specific T cells	signal peptide; B-chain; C-peptide; A-chain; (PPI15-24; PPI2–10)	Escape central and peripheral tolerance; Express IFN-γ; Induce beta cell death via cytotoxic degranulation;	Attack the islets, leading to destruction of beta cells;	Reducing the frequency of PPI-specific T cells and limiting their proliferative potential can delay the progression of T1DM;	(38, 39)
GAD65-specific T cells	GAD114-123;	Present in the early stages of the disease; Shift immune balance towards inflammatory phenotype; Attack pancreatic beta cells;	Trigger inflammation and enhance autoimmune response;	Aid in early diagnosis and intervention; Improve disease management and patient prognosis; Contribute to the development of vaccine-based targeted prevention strategies for T1DM;	(40)
ZnT8-specific T cells	ZnT8186–194 epitope; ZnT8153–161 epitope;	Present in the early stages of the disease; Involved in beta cell destruction;	Participate in diabetes onset under conditions of pancreatic immune impairment;	ZnT8-specific immunotherapy could be a substitute approach for treating T1DM;	(41)
Insulin-specific T cells	B-chain amino acid sequence B:9-23; insulin B15–23;	Prediabetes can be detected; Islet infiltration; Trigger antibody-dependent cytotoxicity against beta cells; Insulin epitope mutations lead to escape of highly pathogenic T cells;	Involved in islet infiltration during prediabetes; Promotes destruction of beta cells; Activates local endothelium to assist penetration of other T cells into the islets;	Understanding mechanisms of escaping negative selection in the thymus helps in developing preventive treatments;	(42, 43)
IGRP-specific T cells	IGRP206-214; IGRP228–236;	Cluster in the islets early; Secrete IFN-γ and granzyme B; The number increases with the progression of islet inflammation and age;	Attacking pancreatic beta cells, inducing destructive insulitis; A crucial component of early islet infiltration.	Monitoring the activity levels of IGRP-specific T cells to assess disease status and predict disease progression, guiding personalized T cell therapy; Lowering cell affinity contributes to disease protection;	(44–46)