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Titolo:
FUNCTIONAL-ACTIVITY OF STAPHYLOCOCCAL-ENTEROTOXIN-A REQUIRES INTERACTIONS WITH BOTH THE ALPHA-CHAIN AND BETA-CHAIN OF HLA-DR
Autore:
DOWD JE; KARR RW; KARP DR;
Indirizzi:
UNIV TEXAS,SW MED CTR,SIMMONS ARTHRIT RES CTR,5323 HARRY HINES BLVD DALLAS TX 75235 UNIV TEXAS,SW MED CTR,SIMMONS ARTHRIT RES CTR DALLAS TX 75235 GD SEARLE & CO ST LOUIS MO 63198
Titolo Testata:
Molecular immunology
fascicolo: 16, volume: 33, anno: 1996,
pagine: 1267 - 1274
SICI:
0161-5890(1996)33:16<1267:FOSRI>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
SHOCK SYNDROME TOXIN-1; MAMMARY-TUMOR VIRUS; HIGH-AFFINITY BINDING; CLASS-II MOLECULES; COMPLEX CLASS-II; HUMAN T-CELLS; BACTERIAL SUPERANTIGENS; 3-DIMENSIONAL STRUCTURE; CLONAL DELETION; IDENTIFICATION;
Keywords:
STAPHYLOCOCCAL ENTEROTOXIN; SUPERANTIGEN; HLA-DR;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
39
Recensione:
Indirizzi per estratti:
Citazione:
J.E. Dowd et al., "FUNCTIONAL-ACTIVITY OF STAPHYLOCOCCAL-ENTEROTOXIN-A REQUIRES INTERACTIONS WITH BOTH THE ALPHA-CHAIN AND BETA-CHAIN OF HLA-DR", Molecular immunology, 33(16), 1996, pp. 1267-1274

Abstract

The staphylococcal enterotoxins, SEA and SEE, bind one zinc atom per molecule of protein. The presence of this metal atom enhances the binding of the toxins to MHC class II molecules, presumably through an interaction with histidine 81 of the beta chain. L cell transfectants expressing HLA-DR1 and HLA-DR7 molecules, with mutations in either the alpha 1 or beta 1 domains, were tested for their ability to bind SEA andpresent it to T cells. Cells expressing DR1 molecules with alanine atpositions 77, 78, 80, 83, 84 and 85, or serine at position 79 could all bind SEA and present it to either polyclonal or monoclonal T cells. Most point mutations within the alpha-helical portion of the DR7 betachain had no effect on binding and presentation. However, substitution of histidine 81 with alanine, glutamate, or aspartate, abrogated SEAbinding as well as T cell stimulation by the superantigen. This effect was also observed when the non-polymorphic aspartate, at position 76was changed to alanine. Mutation of the asparagine at position 82 hadan intermediate effect. Point mutations of the DR alpha chain had little effect on binding of SEA as determined by a flow cytometric assay. However, mutation of lysine at position 39 of the alpha chain and, toa lesser extent methionine at position 36, markedly decreased the ability of SEA to stimulate toxin-responsive mouse T cell hybridomas. Finally, the monoclonal antibody, L243 binds to the alpha chain of HLA-DR, and was able to block T cell activation by SEA without blocking SEA binding. These data support the model whereby HLA-DR has two binding sites for SEA. A low affinity site, present on the alpha chain, is required for T cell stimulation by the superantigen, but is insufficient to mediate toxin binding. High affinity binding of HLA-DR to SEA occurssolely through residues on the beta chain, including both histidine 81 and aspartate 76. (C) 1997 Elsevier Science Ltd.

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Documento generato il 02/07/20 alle ore 22:10:54