Increased islet antigen-specific regulatory and effector CD4+ T cells in healthy individuals with the type 1 diabetes-protective haplotype.

ABSTRACT: The DRB1*15:01-DQB1*06:02 (DR1501-DQ6) haplotype is linked to dominant protection from type 1 diabetes, but the cellular mechanism for this association is unclear. To address this question, we identified multiple DR1501- and DQ6-restricted glutamate decarboxylase 65 (GAD65) and islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP)-specific T cell epitopes. Three of the DR1501/DQ6-restricted epitopes identified were previously reported to be restricted by DRB1*04:01/DRB1*03:01/DQB1*03:02. We also used specific class II tetramer reagents to assess T cell frequencies. Our results indicated that GAD65- and IGRP-specific effector and CD25+CD127-FOXP3+ regulatory CD4+ T cells were present at higher frequencies in individuals with the protective haplotype than those with s

SUBMITTER: Wen X 

PROVIDER: S-EPMC7566980 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature