دورية أكاديمية
Recognition of mRNA Splice Variant and Secretory Granule Epitopes by CD4+ T Cells in Type 1 Diabetes.
| العنوان: | Recognition of mRNA Splice Variant and Secretory Granule Epitopes by CD4+ T Cells in Type 1 Diabetes. |
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| المؤلفون: | Guyer, Perrin, Arribas-Layton, David, Manganaro, Anthony, Speake, Cate, Lord, Sandra, Eizirik, Decio L., Kent, Sally C., Mallone, Roberto, James, Eddie A. |
| المصدر: | Diabetes; Jan2023, Vol. 72 Issue 1, p85-96, 12p |
| مصطلحات موضوعية: | SECRETORY granules, T cells, TYPE 1 diabetes, EPITOPES, RECOGNITION (Psychology), HLA histocompatibility antigens |
| مستخلص: | A recent discovery effort resulted in identification of novel splice variant and secretory granule antigens within the HLA class I peptidome of human islets and documentation of their recognition by CD8+ T cells from peripheral blood and human islets. In the current study, we applied a systematic discovery process to identify novel CD4+ T cell epitopes derived from these candidate antigens. We predicted 145 potential epitopes spanning unique splice junctions and within conventional secretory granule antigens and measured their in vitro binding to DRB1*04:01. We generated HLA class II tetramers for the 35 peptides with detectable binding and used these to assess immunogenicity and isolate T cell clones. Tetramers corresponding to peptides with verified immunogenicity were then used to label T cells specific for these putative epitopes in peripheral blood. T cells that recognize distinct epitopes derived from a cyclin I splice variant, neuroendocrine convertase 2, and urocortin-3 were detected at frequencies that were similar to those of an immunodominant proinsulin epitope. Cells specific for these novel epitopes predominantly exhibited a Th1-like surface phenotype. Among the three epitopes, responses to the cyclin I peptide exhibited a distinct memory profile. Responses to neuroendocrine convertase 2 were detected among pancreatic infiltrating T cells. These results further establish the contribution of unconventional antigens to the loss of tolerance in autoimmune diabetes. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: | Complementary Index |
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