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Titolo:
T cell responses to a human cartilage autoantigen in the context of rheumatoid arthritis-associated and nonassociated HLA-DR4 alleles
Autore:
Cope, AP; Patel, SD; Hall, F; Congia, M; Hubers, HAJM; Verheijden, GF; Boots, AMH; Menon, R; Trucco, M; Rijnders, AWM; Sonderstrup, G;
Indirizzi:
Stanford Univ, Sch Med, Stanford, CA 94305 USA Stanford Univ Stanford CA USA 94305 Univ, Sch Med, Stanford, CA 94305 USA Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA Univ Pittsburgh Pittsburgh PA USA 15260 Sch Med, Pittsburgh, PA 15260 USA NV Organon, NL-5340 BH Oss, Netherlands NV Organon Oss Netherlands NL-5340 BH ganon, NL-5340 BH Oss, Netherlands
Titolo Testata:
ARTHRITIS AND RHEUMATISM
fascicolo: 7, volume: 42, anno: 1999,
pagine: 1497 - 1507
SICI:
0004-3591(199907)42:7<1497:TCRTAH>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
MHC CLASS-II; CHITINASE PROTEIN FAMILY; CRYSTAL-STRUCTURE; TRANSGENIC MICE; MOLECULAR-BASIS; HLA-DR; SUSCEPTIBILITY; PEPTIDE; SEQUENCE; RECEPTOR;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
41
Recensione:
Indirizzi per estratti:
Indirizzo: Sonderstrup, G Stanford Univ, Sch Med, Room 345,Fairchild Bldg, Stanford, CA 94305 USA Stanford Univ Room 345,Fairchild Bldg Stanford CA USA 94305
Citazione:
A.P. Cope et al., "T cell responses to a human cartilage autoantigen in the context of rheumatoid arthritis-associated and nonassociated HLA-DR4 alleles", ARTH RHEUM, 42(7), 1999, pp. 1497-1507

Abstract

Objective. To analyze the CD4+ T cell responses to the human cartilage antigen glycoprotein-39 (HCgp-39) in the context of rheumatoid arthritis (RA)-associated (DR alpha beta 1*0401) and nonassociated (DR alpha beta 1*0402) HLA class II molecules. Methods, Large numbers of HCgp-39-specific T cell hybridomas were generated following immunization of HLA-DR4/human CD4 transgenic, murine major histocompatibility complex class II deficient mice with native HCgp-39. Fine epitope mapping of DR alpha beta 1*0401 and DR alpha beta 1*0402-restricted Tcell hybridomas was performed using overlapping synthetic peptides. Antigen-specific cytokine production by lymph node T cells was evaluated after immunization with native antigen. Proliferative T cell responses of healthy human subjects were compared with the T cell responses of patients with active RA using HCgp-39 epitopes defined in HLA-DR4 transgenic mice. Results, CD4+ T cells from DR alpha beta 1*0401 and DR alpha beta 1*0402 transgenic mice identified completely different immunodominant peptide epitopes of HCgp-39, and this was not explained by known DR4-binding motifs or direct peptide-binding studies, DR alpha beta 1*0401-restricted, antigen-specific T cells produced significantly more interferon-gamma and tumor necrosis factor alpha in response to HCgp-39 than did T cells from DR alpha beta 1*0402 transgenic mice. Finally, HCgp-39 peptides defined in DR alpha beta 1*0401 transgenic mice stimulated T cells from HLA-DR4 positive human subjects and RA patients, but not T cells from HLA-DR4 negative individuals. Conclusion. T cell epitopes of HCgp-39 that were defined in HLA-DR4 transgenic mice stimulated T cells from human subjects carrying RA-associated HLA-DR4 alleles. HLA-DR4 molecules may influence the disease process in RA both by presentation of selected peptide epitopes and by promoting the production of proinflammatory cytokines in synovial-joints.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/12/20 alle ore 22:39:32