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Titolo:
Molecular requirements for T cell recognition by a major histocompatibility complex class II-restricted T cell receptor: The involvement of the fourth hypervariable loop of the V alpha domain
Autore:
Thatte, J; Qadri, A; Radu, C; Ward, ES;
Indirizzi:
Univ Texas, SW Med Ctr, Ctr Immunol, Dallas, TX 75235 USA Univ Texas Dallas TX USA 75235 Med Ctr, Ctr Immunol, Dallas, TX 75235 USA Univ Texas, SW Med Ctr, Dept Microbiol, Dallas, TX 75235 USA Univ Texas Dallas TX USA 75235 Ctr, Dept Microbiol, Dallas, TX 75235 USA
Titolo Testata:
JOURNAL OF EXPERIMENTAL MEDICINE
fascicolo: 3, volume: 189, anno: 1999,
pagine: 509 - 519
SICI:
0022-1007(19990201)189:3<509:MRFTCR>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
MYELIN BASIC-PROTEIN; ANTIGEN RECEPTOR; BETA-CHAIN; CRYSTAL-STRUCTURE; SIGNAL-TRANSDUCTION; ANTAGONIST LIGANDS; KINASE P56LCK; CD4; MHC; PEPTIDE;
Keywords:
T cell receptor; V alpha domain; fourth hypervariable loop; antigen recognition; CD4 coreceptor;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
71
Recensione:
Indirizzi per estratti:
Indirizzo: Ward, ES Univ5Texas, SW Med Ctr, Ctr Immunol, 6000 Harry Hines Blvd, Dallas, TX 7523 Univ Texas 6000 Harry Hines Blvd Dallas TX USA 75235 las, TX 7523
Citazione:
J. Thatte et al., "Molecular requirements for T cell recognition by a major histocompatibility complex class II-restricted T cell receptor: The involvement of the fourth hypervariable loop of the V alpha domain", J EXP MED, 189(3), 1999, pp. 509-519

Abstract

The role of two central residues (K68, E69) of the fourth hypervariable loop of the Vol domain (HV4 alpha) in antigen recognition by an MHC class II-restricted T cell receptor (TCR) has been analyzed. The TCR recognizes the NH2-terminal peptide of myelin basic protein (Ac1-11, acetylated at NH2 terminus) associated with the class II MHC molecule I-A(u). Lysine 68 (K68) and glutamic acid 69 (E69) of HV4 alpha have been mutated both individually and simultaneously to alanine (K68A, E69A). The responsiveness of transfectants bearing wild-type and mutated TCRs to Ac1-11-I-A(u) complexes has been analyzed in the presence and absence of expression of the coreceptor CD4. The data demonstrate that in die absence of CD4 expression, K68 plays a central role in antigen responsiveness. In contrast, the effect of mutating E69to alanine is less marked. CD4 coexpression can partially compensate for the loss of activity of the K68A mutant transfectants, resulting in responses that, relative to those of the wild-type transfectants, are highly sensitive to anti-CD4 antibody blockade. The observations support models of T cell activation in which both the affinity of the TCR for cognate ligand and the involvement of coreceptors determine the outcome of the T cell-antigen-presenting cell interaction.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/11/20 alle ore 10:00:20