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Human CD8 responses to a complete epitope set from preproinsulin: implications for approaches to epitope discovery

Baker, Caroline, Petrich de Marquesini, Liliana G., Bishop, Amanda J., Hedges, Alan J., Dayan, Colin Mark and Wong, Florence Susan 2008. Human CD8 responses to a complete epitope set from preproinsulin: implications for approaches to epitope discovery. Journal of Clinical Immunology 28 (4) , pp. 350-360. 10.1007/s10875-008-9177-4

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Purpose In this study, we explored the breadth of CD8 T cell reactivity to preproinsulin (PPI) in type 1 diabetes. Materials and Methods We tested a complete peptide set in pools covering all 406 potential 8–11mer epitopes of PPI and 61 algorithm-predicted human leukocyte antigen (HLA)-A2-specific epitopes (15 pools) from islet-specific glucose-6-phophatase catalytic subunit-related protein (IGRP), using a CD8-specific granzyme B enzyme-linked immunosorbent spot assay. Results Responses were seen to 64 of the 102 PPI pools in two or more newly diagnosed patients (63%) compared to 11 pools in the control subjects (11%, p < 0.0001, Fisher’s exact test). We identified five pools containing 20 peptides, which distinguished patients from control subjects, most of which had predicted low-affinity binding to HLA class I molecules. In contrast, fewer (5 of 15 = 33%) IGRP peptide pools, selected by higher binding affinity for HLA-A2 (present in seven of eight patients and five of seven control subjects), stimulated responses in two or more patients, and none stimulated responses in more than two control subjects (p = 0.042, Fisher’s exact test). Conclusion Thus, we conclude that CD8 T cell reactivity to PPI in patients with type 1 diabetes can be much broader than shown previously and more diverse than seen in control subjects. Furthermore, responses were often stimulated by peptides with low predicted HLA-binding affinities.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > R Medicine (General)
Uncontrolled Keywords: type 1 diabetes, autoimmunity, human, CD8 T cells
Publisher: Springer
ISSN: 0271-9142
Last Modified: 04 Jun 2017 03:35

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