Distinct sets of alphabeta TCRs confer similar recognition of tumor antigen NY-ESO-1157-165 by interacting with its central Met/Trp residues.


Autoria(s): Derré L.; Bruyninx M.; Baumgaertner P.; Ferber M.; Schmid D.; Leimgruber A.; Zoete V.; Romero P.; Michielin O.; Speiser D.E.; Rufer N.
Data(s)

2008

Resumo

Naturally acquired immune responses against human cancers often include CD8(+) T cells specific for the cancer testis antigen NY-ESO-1. Here, we studied T cell receptor (TCR) primary structure and function of 605 HLA-A*0201/NY-ESO-1(157-165)-specific CD8 T cell clones derived from five melanoma patients. We show that an important proportion of tumor-reactive T cells preferentially use TCR AV3S1/BV8S2 chains, with remarkably conserved CDR3 amino acid motifs and lengths in both chains. All remaining T cell clones belong to two additional sets expressing BV1 or BV13 TCRs, associated with alpha-chains with highly diverse VJ usage, CDR3 amino acid sequence, and length. Yet, all T cell clonotypes recognize tumor antigen with similar functional avidity. Two residues, Met-160 and Trp-161, located in the middle region of the NY-ESO-1(157-165) peptide, are critical for recognition by most of the T cell clonotypes. Collectively, our data show that a large number of alphabeta TCRs, belonging to three distinct sets (AVx/BV1, AV3/BV8, AVx/BV13) bind pMHC with equal antigen sensitivity and recognize the same peptide motif. Finally, this in-depth study of recognition of a self-antigen suggests that in part similar biophysical mechanisms shape TCR repertoires toward foreign and self-antigens.

Identificador

http://serval.unil.ch/?id=serval:BIB_9C31B2F8BC85

isbn:1091-6490 (Electronic)

pmid:18809922

doi:10.1073/pnas.0807954105

isiid:000261914300034

http://my.unil.ch/serval/document/BIB_9C31B2F8BC85.pdf

http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_9C31B2F8BC856

Idioma(s)

en

Direitos

info:eu-repo/semantics/openAccess

Fonte

Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 39, pp. 15010-15015

Palavras-Chave #Amino Acid Motifs; Amino Acid Sequence; CD8-Positive T-Lymphocytes/immunology; Clone Cells; Conserved Sequence; Humans; Melanoma/immunology; Methionine/chemistry; Molecular Sequence Data; Neoplasm Proteins/immunology; Peptide Fragments/immunology; Receptors, Antigen, T-Cell, alpha-beta/chemistry; Receptors, Antigen, T-Cell, alpha-beta/classification; Skin Neoplasms/immunology; Threonine/chemistry; Transcription, Genetic
Tipo

info:eu-repo/semantics/article

article