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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 ORCID: and Wong, Florence Susan ORCID: 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: 19 Oct 2022 10:07

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