PMID- 22069251
OWN - NLM
STAT- MEDLINE
DCOM- 20120325
LR  - 20191210
IS  - 1520-7560 (Electronic)
IS  - 1520-7552 (Linking)
VI  - 27
IP  - 8
DP  - 2011 Nov
TI  - 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.
PG  - 720-6
LID - 10.1002/dmrr.1243 [doi]
AB  - BACKGROUND: Identification of T-cell reactivity to beta-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-gamma 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 beta-cell epitopes than CD8+ T-cell 
      interferon-gamma 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-gamma 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.
CI  - Copyright (c) 2011 John Wiley & Sons, Ltd.
FAU - Mallone, R
AU  - Mallone R
AD  - INSERM U986, DeAR Lab Avenir, Saint Vincent de Paul Hospital, and Paris Descartes 
      University, Paris, France. Roberto.Mallone@inserm.fr
FAU - Scotto, M
AU  - Scotto M
FAU - Janicki, C N
AU  - Janicki CN
FAU - James, E A
AU  - James EA
FAU - Fitzgerald-Miller, L
AU  - Fitzgerald-Miller L
FAU - Wagner, R
AU  - Wagner R
FAU - Gottlieb, P
AU  - Gottlieb P
FAU - Thorpe, J
AU  - Thorpe J
FAU - Jospe, N
AU  - Jospe N
FAU - Durinovic-Bello, I
AU  - Durinovic-Bello I
FAU - Boitard, C
AU  - Boitard C
FAU - Lou, O
AU  - Lou O
FAU - Dayan, C M
AU  - Dayan CM
FAU - Wong, F S
AU  - Wong FS
CN  - T-Cell Workshop Committee, Immunology of Diabetes Society
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
PT  - Validation Study
PL  - England
TA  - Diabetes Metab Res Rev
JT  - Diabetes/metabolism research and reviews
JID - 100883450
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (HLA-A Antigens)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Insulin)
RN  - 0 (Protein Precursors)
RN  - 61116-24-3 (preproinsulin)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 4.1.1.15 (Glutamate Decarboxylase)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Diabetes Mellitus, Type 1/*immunology
MH  - Enzyme-Linked Immunospot Assay
MH  - Epitopes, T-Lymphocyte/*immunology
MH  - Glutamate Decarboxylase/immunology
MH  - HLA-A Antigens/immunology
MH  - Histocompatibility Antigens Class I/*immunology
MH  - Humans
MH  - Insulin/*immunology
MH  - Interferon-gamma/immunology
MH  - Protein Precursors/*immunology
FIR - Schloot, N C
IR  - Schloot NC
FIR - Brooks-Worrell, B
IR  - Brooks-Worrell B
FIR - Cilio, C
IR  - Cilio C
FIR - Mannering, S
IR  - Mannering S
FIR - Tree, T
IR  - Tree T
FIR - Zhou, Z
IR  - Zhou Z
EDAT- 2011/11/10 06:00
MHDA- 2012/03/27 06:00
CRDT- 2011/11/10 06:00
PHST- 2011/11/10 06:00 [entrez]
PHST- 2011/11/10 06:00 [pubmed]
PHST- 2012/03/27 06:00 [medline]
AID - 10.1002/dmrr.1243 [doi]
PST - ppublish
SO  - Diabetes Metab Res Rev. 2011 Nov;27(8):720-6. doi: 10.1002/dmrr.1243.