Antigen-Specific T Cell Analysis Reveals That Active Immune Responses to β Cell Antigens Are Focused on a Unique Set of Epitopes

• Published in: The Journal of immunology (1950) Vol. 199; no. 1; pp. 91 - 96
• Main Authors: Yang, Junbao, Wen, Xiaomin, Xu, Hengyu, Torres-Chinn, Nadia, Speake, Cate, Greenbaum, Carla J, Nepom, Gerald T, Kwok, William W
• Format: Journal Article
• Language: English
• Published: United States American Association of Immunologists 01.07.2017
• Subjects: Adolescent; ADP-ribosyl Cyclase 1 - genetics; ADP-ribosyl Cyclase 1 - immunology; Adult; Antigens; Autoantigens - immunology; Cation Transport Proteins - chemistry; Cation Transport Proteins - immunology; CD38 antigen; CD4 antigen; CD4-Positive T-Lymphocytes - chemistry; CD4-Positive T-Lymphocytes - immunology; CD40 Ligand - genetics; CD40 Ligand - immunology; CD40L protein; Cell activation; Child; Diabetes; Diabetes mellitus; Diabetes Mellitus, Type 1 - immunology; Epitope Mapping; Epitopes, T-Lymphocyte - chemistry; Epitopes, T-Lymphocyte - genetics; Epitopes, T-Lymphocyte - immunology; Epitopes, T-Lymphocyte - metabolism; Female; Humans; Immune response; Immunologic Memory; Immunological memory; Insulin - immunology; Insulin-Secreting Cells - immunology; Leukocyte Common Antigens - genetics; Leukocyte Common Antigens - immunology; Lymphocyte Activation; Lymphocytes; Lymphocytes T; Male; Membrane Glycoproteins - genetics; Membrane Glycoproteins - immunology; Memory cells; Middle Aged; Preproinsulin; Protein Precursors - immunology; Young Adult; Zinc Transporter 8
• ISSN: 0022-1767; 1550-6606; 1550-6606
• DOI: 10.4049/jimmunol.1601570

CD38 is an activation marker that is present on recently activated T cells, but absent on resting memory T cells. In this study, we show that CD45RO+CD38+ β cell Ag-specific CD4+ T cells were present at higher frequencies in type 1 diabetes subjects compared with those in healthy subjects. These results imply an ongoing β cell immunity years after onset of diabetes and suggest these activated T cells have an active role in the disease process. The Ag specificities of these activated T cells were determined by a novel CD154 T cell epitope mapping assay. Although each patient usually had a unique set of epitopes recognized by these T cells, two epitopes, DR0401-restricted modified preproinsulin peptide 78–90K88S and zinc transport 8 266–285, were repeatedly identified in multiple subjects. Identifying these T cells and their specific antigenic epitopes might provide immunotherapeutic targets for personalized therapies.