Abstract
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.
Copyright © 2017 by The American Association of Immunologists, Inc.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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ADP-ribosyl Cyclase 1 / genetics
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ADP-ribosyl Cyclase 1 / immunology
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Adolescent
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Adult
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Autoantigens / immunology
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CD4-Positive T-Lymphocytes / chemistry
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CD4-Positive T-Lymphocytes / immunology*
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CD40 Ligand / genetics
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CD40 Ligand / immunology
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Cation Transport Proteins / chemistry
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Cation Transport Proteins / immunology
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Child
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Diabetes Mellitus, Type 1 / immunology
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Epitope Mapping
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Epitopes, T-Lymphocyte / chemistry*
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Epitopes, T-Lymphocyte / genetics
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Epitopes, T-Lymphocyte / immunology*
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Epitopes, T-Lymphocyte / metabolism
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Female
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Humans
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Immunologic Memory
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Insulin / immunology
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Insulin-Secreting Cells / immunology*
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Leukocyte Common Antigens / genetics
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Leukocyte Common Antigens / immunology
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Lymphocyte Activation
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Male
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / immunology
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Middle Aged
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Protein Precursors / immunology
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Young Adult
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Zinc Transporter 8
Substances
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Autoantigens
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Cation Transport Proteins
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Epitopes, T-Lymphocyte
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Insulin
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Membrane Glycoproteins
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Protein Precursors
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SLC30A8 protein, human
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Zinc Transporter 8
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CD40 Ligand
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preproinsulin
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Leukocyte Common Antigens
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PTPRC protein, human
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CD38 protein, human
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ADP-ribosyl Cyclase 1