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Titolo:
IDENTIFICATION OF NATURALLY PROCESSED T-CELL EPITOPES FROM GLUTAMIC-ACID DECARBOXYLASE PRESENTED IN THE CONTEXT OF HLA-DR ALLELES BY T-LYMPHOCYTES OF RECENT-ONSET IDDM PATIENTS
Autore:
ENDL J; OTTO H; JUNG G; DREISBUSCH B; DONIE F; STAHL P; ELBRACHT R; SCHMITZ G; MEINL E; HUMMEL M; ZIEGLER AG; WANK R; SCHENDEL DJ;
Indirizzi:
BOEHRINGER MANNHEIM GMBH,RES CTR,NONNENWALD 2 D-82377 PENZBERG GERMANY UNIV TUBINGEN,INST ORGAN CHEM D-72076 TUBINGEN GERMANY UNIV REGENSBURG,INST CLIN CHEM D-93053 REGENSBURG GERMANY UNIV ERLANGEN NURNBERG,INST CLIN & MOL VIROL D-91054 ERLANGEN GERMANY ACAD HOSP MUNCHEN SCHWABING,DIABET RES INST D-80804 MUNICH GERMANY UNIV MUNICH,INST IMMUNOL D-80336 MUNICH GERMANY
Titolo Testata:
The Journal of clinical investigation
fascicolo: 10, volume: 99, anno: 1997,
pagine: 2405 - 2415
SICI:
0021-9738(1997)99:10<2405:IONPTE>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
DEPENDENT DIABETES-MELLITUS; MYELIN BASIC-PROTEIN; CLASS-II MOLECULES; COXSACKIE-VIRUS; ANTIBODIES; AUTOIMMUNITY; IMMUNITY; PEPTIDES; DISEASE; HLA-DR2;
Keywords:
T CELL EPITOPES; GLUTAMIC ACID DECARBOXYLASE; AUTOIMMUNITY; PEPTIDE AUTOANTIGENS; COXSACKIE VIRUS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
36
Recensione:
Indirizzi per estratti:
Citazione:
J. Endl et al., "IDENTIFICATION OF NATURALLY PROCESSED T-CELL EPITOPES FROM GLUTAMIC-ACID DECARBOXYLASE PRESENTED IN THE CONTEXT OF HLA-DR ALLELES BY T-LYMPHOCYTES OF RECENT-ONSET IDDM PATIENTS", The Journal of clinical investigation, 99(10), 1997, pp. 2405-2415

Abstract

Glutamic acid decarboxylase (GAD) has been defined as a major target antigen in insulin-dependent diabetes mellitus (IDDM). To identify themolecular ligands triggering a T cell response to GAD, a panel of human GAD65-specific T lymphocyte lines was generated from peripheral blood of three recent onset IDDM patients. All lines derived from a patient expressing the high-risk-conferring HLA-DR0301/*0401 haplotypes recognized a single epitope localized between amino acid positions 270 and 283 of GAD65, a stretch that is located in close proximity to the homology region shared with Coxsackie virus P2-C protein. All lines with this specificity were restricted to the DRA, B10401 product of the DR4 haplotype. Analysis of the GAD-specific T cell response in a second patient homozygous for DR4 haplotypes demonstrated that the same DRA, B10401 allele selected T cells specific for a different determinant. The T cell response profile in a third patient showed that DR1501/*1601-encoding haplotypes could present at least three different epitopes to GAD65-specific T lymphocytes. One of these epitopes was presented by a DR allele associated with the resistance-conferring DRB11501 haplotype. GAD-specific T cell lines could not be isolated from HLA class II-matched normal individuals. Our data reveal that (a) the T cell response to GAD65 is quite heterogenous in recent on-set IDDM patients; (b) HLA-DR, not DQ, seems to be the principal restriction element used by T cells present at the onset of the disease; and (c) T cells responding to epitopes containing identical sequences to Coxsackie virus P2-C protein were not detected.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/11/20 alle ore 15:52:23