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Titolo:
Kinetics and thermodynamics of T cell receptor-autoantigen interactions inmurine experimental autoimmune encephalomyelitis
Autore:
Garcia, KC; Radu, CG; Ho, J; Ober, RJ; Ward, ES;
Indirizzi:
Univ Texas, SW Med Ctr, Ctr Immunol, Dallas, TX 75390 USA Univ Texas Dallas TX USA 75390 Med Ctr, Ctr Immunol, Dallas, TX 75390 USA Univ Texas, SW Med Ctr, Ctr Canc Immunobiol, Dallas, TX 75390 USA Univ Texas Dallas TX USA 75390 Ctr Canc Immunobiol, Dallas, TX 75390 USA Stanford Univ, Sch Med, Dept Microbiol & Immunol, Stanford, CA 94305 USA Stanford Univ Stanford CA USA 94305 iol & Immunol, Stanford, CA 94305 USA Stanford Univ, Sch Med, Dept Biol Struct, Stanford, CA 94305 USA Stanford Univ Stanford CA USA 94305 t Biol Struct, Stanford, CA 94305 USA
Titolo Testata:
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
fascicolo: 12, volume: 98, anno: 2001,
pagine: 6818 - 6823
SICI:
0027-8424(20010605)98:12<6818:KATOTC>2.0.ZU;2-2
Fonte:
ISI
Lingua:
ENG
Soggetto:
MYELIN BASIC-PROTEIN; MAJOR HISTOCOMPATIBILITY COMPLEX; CLASS-II MHC; TRANSGENIC MICE; PEPTIDE-MHC; ANTIGEN RECOGNITION; MOLECULAR MIMICRY; CRYSTAL-STRUCTURE; VIRAL PEPTIDE; SELF-PEPTIDE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
53
Recensione:
Indirizzi per estratti:
Indirizzo: Ward, ES Univ Texas, SW Med Ctr, Ctr Immunol, Dallas, TX 75390 USA Univ Texas Dallas TX USA 75390 Ctr Immunol, Dallas, TX 75390 USA
Citazione:
K.C. Garcia et al., "Kinetics and thermodynamics of T cell receptor-autoantigen interactions inmurine experimental autoimmune encephalomyelitis", P NAS US, 98(12), 2001, pp. 6818-6823

Abstract

In the current study, cellular and molecular approaches have been used to analyze the biophysical nature of T cell receptor (TCR)peptide MHC(pMHC) interactions for two autoreactive TCRs. These two TCRs recognize the N-terminal epitope of myelin basic: protein (MBP1-11) bound to the MHC class II protein. I-AU, and are associated with murine experimental autoimmune encephalomyelitis. Mice transgenic for the TCRs have been generated and characterized in other laboratories. These analyses indicate that the mice either develop encephalomyelitis spontaneously (172.10 TCR) or only if immunized with autoantigen in adjuvant (1934.4 TCR). Here, we show that the 172.10 TCR binds MBP1-11:I-A(u) with a 4-5-fold higher affinity than the 1934.4 TCR, Consistent with the higher affinity, 172.10 T hybridoma cells are significantlymore responsive to autoantigen than 1934.4 cells. The interaction of the 172.10 TCR with cognate ligand is more entropically unfavorable than that ofthe 1934.4 TCR, indicating that the 172.10 TCR undergoes greater conformational rearrangements upon ligand binding. The studies therefore suggest a correlation between the strength and plasticity of a TCR-pMHC interaction and the frequency of spontaneous disease in the corresponding TCR transgenic mice. The comparative analysis of these two TCRs has implications for understanding autoreactive T cell recognition and activation.

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Documento generato il 24/11/20 alle ore 13:25:55