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- Title
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.
- Authors
Mallone, R.; Scotto, M.; Janicki, C. N.; James, E. A.; Fitzgerald-Miller, L.; Wagner, R.; Gottlieb, P.; Thorpe, J.; Jospe, N.; Durinovic-Bellò, I.; Boitard, C.; Lou, O.; Dayan, C. M.; Wong, F. S.
- 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; PPI $\def\endash{\hbox{--}} _{\rm{A12\endash 20}}$ and PPI $\def\endash{\hbox{--}} _{\rm{B10\endash 18}}$) 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. Copyright © 2011 John Wiley & Sons, Ltd.
- Publication
Diabetes/Metabolism Research & Reviews, 2011, Vol 27, Issue 8, p720
- ISSN
1520-7552
- Publication type
Article
- DOI
10.1002/dmrr.1243