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Immunology of diabetes society T-Cell workshop: HLA class I tetramer-directed epitope validation initiative T-Cell workshop report-HLA class I tetramer validation initiative

Mallone, R., Scotto, M., Janicki, Claire Nicola, James, E. A., Fitzgerald-Miller, L., Wagner, R., Gottlieb, P., Thorpe, J, Jospe, N., Durinovic-Bellò, I., Boitard, C., Lou, O., Dayan, Colin Mark and Wong, Florence Susan 2011. Immunology of diabetes society T-Cell workshop: HLA class I tetramer-directed epitope validation initiative T-Cell workshop report-HLA class I tetramer validation initiative. Diabetes/Metabolism Research and Reviews 27 (8) , pp. 720-726. 10.1002/dmrr.1243

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Abstract

BACKGROUND: Identification of T-cell reactivity to β-cell antigen epitopes is an important goal for studying pathogenesis and for designing and monitoring of immunotherapeutic interventions in type 1 diabetes (T1D). METHODS: We performed a multicentre validation of known human leukocyte antigen (HLA) class I CD8+ T-cell epitopes. To this end, peripheral blood T-cell responses were measured in 35 recently (<2 years) diagnosed HLA-A*02:01+ T1D patients using blind-coded HLA-A2 tetramers (TMrs) and pentamers (PMrs), encompassing two epitopes of preproinsulin (PPI; PPIA12-20 and PPIB10-18) and two epitopes of glutamic acid decarboxylase (GAD; GAD114-122 and GAD536-545). We also compared the readout of TMrs and PMrs with a CD8+ T-cell interferon-γ enzyme-linked immunospot assay. RESULTS: Despite the minute frequencies of autoreactive cells detected by TMrs/PMrs, most (73-77%) T1D patients had responses to one or more of the epitopes used. All four epitopes were recognized by T1D patients, with a prevalence ranging from 5 to 25%. TMrs and PMrs detected more positive responses to the β-cell epitopes than CD8+ T-cell interferon-γ enzyme-linked immunospot. However, concordance between positive responses to TMrs and PMrs was limited. CONCLUSIONS: Using a multicentre blind-coded setup and three different T-cell assays, we have validated PPI and GAD epitopes as commonly recognized CD8+ T-cell targets in recently diagnosed T1D patients. Both TMrs and PMrs showed higher detection sensitivity than the CD8+ T-cell interferon-γ enzyme-linked immunospot assay. However, there are some important methodological issues that need to be addressed in using these sensitive techniques for detecting low frequency responses.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > R Medicine (General)
Uncontrolled Keywords: antigen, autoimmunity, ELISpot, GAD, insulin
Additional Information: Diabetes/Metabolism Research and Reviews Special Issue: Proceedings of the 11th Annual Meeting of the Immunology of Diabetes Society, Incheon, Korea
Publisher: Wiley
ISSN: 1520-7552
Last Modified: 04 Jun 2017 03:31
URI: http://orca.cf.ac.uk/id/eprint/22336

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