PMID- 18311511
OWN - NLM
STAT- MEDLINE
DCOM- 20080923
LR  - 20211020
IS  - 0271-9142 (Print)
IS  - 0271-9142 (Linking)
VI  - 28
IP  - 4
DP  - 2008 Jul
TI  - Human CD8 responses to a complete epitope set from preproinsulin: implications 
      for approaches to epitope discovery.
PG  - 350-60
LID - 10.1007/s10875-008-9177-4 [doi]
AB  - 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.
FAU - Baker, Caroline
AU  - Baker C
AD  - Department of Cellular and Molecular Medicine, School of Medical Sciences, 
      University of Bristol, University Walk, Bristol BS8 1TD, UK.
FAU - Petrich de Marquesini, Liliana G
AU  - Petrich de Marquesini LG
FAU - Bishop, Amanda J
AU  - Bishop AJ
FAU - Hedges, Alan J
AU  - Hedges AJ
FAU - Dayan, Colin M
AU  - Dayan CM
FAU - Wong, F Susan
AU  - Wong FS
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080229
PL  - Netherlands
TA  - J Clin Immunol
JT  - Journal of clinical immunology
JID - 8102137
RN  - 0 (Autoantibodies)
RN  - 0 (Autoantigens)
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (ICA512 autoantibody)
RN  - 0 (Insulin)
RN  - 0 (Peptide Library)
RN  - 0 (Protein Precursors)
RN  - 61116-24-3 (preproinsulin)
RN  - EC 3.1.3.9 (Glucose-6-Phosphatase)
RN  - EC 3.1.3.9. (G6PC2 protein, human)
RN  - EC 3.4.21.- (Granzymes)
RN  - EC 4.1.1.15 (Glutamate Decarboxylase)
SB  - IM
MH  - Adult
MH  - Autoantibodies/blood
MH  - Autoantigens/immunology
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Diabetes Mellitus, Type 1/*immunology
MH  - Epitopes, T-Lymphocyte/*immunology
MH  - Female
MH  - Glucose-6-Phosphatase/immunology
MH  - Glutamate Decarboxylase/immunology
MH  - Granzymes/metabolism
MH  - Humans
MH  - Insulin/*immunology
MH  - Lymphocyte Activation/immunology
MH  - Male
MH  - Peptide Library
MH  - Protein Precursors/*immunology
EDAT- 2008/03/04 09:00
MHDA- 2008/09/24 09:00
CRDT- 2008/03/04 09:00
PHST- 2007/10/26 00:00 [received]
PHST- 2008/01/15 00:00 [accepted]
PHST- 2008/03/04 09:00 [pubmed]
PHST- 2008/09/24 09:00 [medline]
PHST- 2008/03/04 09:00 [entrez]
AID - 10.1007/s10875-008-9177-4 [doi]
PST - ppublish
SO  - J Clin Immunol. 2008 Jul;28(4):350-60. doi: 10.1007/s10875-008-9177-4. Epub 2008 
      Feb 29.