Structural basis for enabling T-cell receptor diversity within biased virus-specific CD8+ T-cell responses

E Bridie Day, Carole Guillonneau, Stephanie Gras, Nicole L La Gruta, Dario Vignali, Peter Doherty, Anthony Purcell, Jamie Rossjohn, Stephen Turner

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Pathogen-specific responses are characterized by preferred profiles of peptide+class I MHC (pMHCI) glycoprotein-specific T-cell receptor (TCR) Variable (V)-region use. How TCRV-region bias impacts TCRalphabeta heterodimer selection and resultant diversity is unclear. The D(b)PA(224)-specific TCR repertoire in influenza A virus-infected C57BL/6J (B6) mice exhibits a preferred TCRV-region bias toward the TRBV29 gene segment and an optimal complementarity determining region (CDR3) beta-length of 6 aa. Despite these restrictions, D(b)PA(224)-specific BV29(+) T cells use a wide array of unique CDR3beta sequences. Structural characterization of a single, TRBV29(+)D(b)P(A224)-specific TCRalphabeta-pMHCI complex demonstrated that CDR3alpha amino acid side chains made specific peptide interactions, but the CDR3beta main chain exclusively contacted peptides. Thus, length but not amino acid sequence was key for recognition and flexibility in Vbeta-region use. In support of this hypothesis, retrovirus expression of the D(b)PA(224)-specific TCRValpha-chain was used to constrain pairing within a naive/immune epitope-specific repertoire. The retrogenic TCRValpha paired with a diversity of CDR3betas in the context of a preferred TCRVbeta spectrum. Overall, these data provide an explanation for the combination of TCRV region bias and diversity within selected repertoires, even as they maintain exquisite pMHCI specificity.
Original languageEnglish
Pages (from-to)9536 - 9541
Number of pages6
JournalProceedings of the National Academy of Sciences
Volume108
Issue number23
DOIs
Publication statusPublished - 2011

Cite this

@article{10773c4e53564d2f9e3e84f23c29c52c,
title = "Structural basis for enabling T-cell receptor diversity within biased virus-specific CD8+ T-cell responses",
abstract = "Pathogen-specific responses are characterized by preferred profiles of peptide+class I MHC (pMHCI) glycoprotein-specific T-cell receptor (TCR) Variable (V)-region use. How TCRV-region bias impacts TCRalphabeta heterodimer selection and resultant diversity is unclear. The D(b)PA(224)-specific TCR repertoire in influenza A virus-infected C57BL/6J (B6) mice exhibits a preferred TCRV-region bias toward the TRBV29 gene segment and an optimal complementarity determining region (CDR3) beta-length of 6 aa. Despite these restrictions, D(b)PA(224)-specific BV29(+) T cells use a wide array of unique CDR3beta sequences. Structural characterization of a single, TRBV29(+)D(b)P(A224)-specific TCRalphabeta-pMHCI complex demonstrated that CDR3alpha amino acid side chains made specific peptide interactions, but the CDR3beta main chain exclusively contacted peptides. Thus, length but not amino acid sequence was key for recognition and flexibility in Vbeta-region use. In support of this hypothesis, retrovirus expression of the D(b)PA(224)-specific TCRValpha-chain was used to constrain pairing within a naive/immune epitope-specific repertoire. The retrogenic TCRValpha paired with a diversity of CDR3betas in the context of a preferred TCRVbeta spectrum. Overall, these data provide an explanation for the combination of TCRV region bias and diversity within selected repertoires, even as they maintain exquisite pMHCI specificity.",
author = "Day, {E Bridie} and Carole Guillonneau and Stephanie Gras and {La Gruta}, {Nicole L} and Dario Vignali and Peter Doherty and Anthony Purcell and Jamie Rossjohn and Stephen Turner",
year = "2011",
doi = "10.1073/pnas.1106851108",
language = "English",
volume = "108",
pages = "9536 -- 9541",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "23",

}

Structural basis for enabling T-cell receptor diversity within biased virus-specific CD8+ T-cell responses. / Day, E Bridie; Guillonneau, Carole; Gras, Stephanie; La Gruta, Nicole L; Vignali, Dario; Doherty, Peter; Purcell, Anthony; Rossjohn, Jamie; Turner, Stephen.

In: Proceedings of the National Academy of Sciences, Vol. 108, No. 23, 2011, p. 9536 - 9541.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Structural basis for enabling T-cell receptor diversity within biased virus-specific CD8+ T-cell responses

AU - Day, E Bridie

AU - Guillonneau, Carole

AU - Gras, Stephanie

AU - La Gruta, Nicole L

AU - Vignali, Dario

AU - Doherty, Peter

AU - Purcell, Anthony

AU - Rossjohn, Jamie

AU - Turner, Stephen

PY - 2011

Y1 - 2011

N2 - Pathogen-specific responses are characterized by preferred profiles of peptide+class I MHC (pMHCI) glycoprotein-specific T-cell receptor (TCR) Variable (V)-region use. How TCRV-region bias impacts TCRalphabeta heterodimer selection and resultant diversity is unclear. The D(b)PA(224)-specific TCR repertoire in influenza A virus-infected C57BL/6J (B6) mice exhibits a preferred TCRV-region bias toward the TRBV29 gene segment and an optimal complementarity determining region (CDR3) beta-length of 6 aa. Despite these restrictions, D(b)PA(224)-specific BV29(+) T cells use a wide array of unique CDR3beta sequences. Structural characterization of a single, TRBV29(+)D(b)P(A224)-specific TCRalphabeta-pMHCI complex demonstrated that CDR3alpha amino acid side chains made specific peptide interactions, but the CDR3beta main chain exclusively contacted peptides. Thus, length but not amino acid sequence was key for recognition and flexibility in Vbeta-region use. In support of this hypothesis, retrovirus expression of the D(b)PA(224)-specific TCRValpha-chain was used to constrain pairing within a naive/immune epitope-specific repertoire. The retrogenic TCRValpha paired with a diversity of CDR3betas in the context of a preferred TCRVbeta spectrum. Overall, these data provide an explanation for the combination of TCRV region bias and diversity within selected repertoires, even as they maintain exquisite pMHCI specificity.

AB - Pathogen-specific responses are characterized by preferred profiles of peptide+class I MHC (pMHCI) glycoprotein-specific T-cell receptor (TCR) Variable (V)-region use. How TCRV-region bias impacts TCRalphabeta heterodimer selection and resultant diversity is unclear. The D(b)PA(224)-specific TCR repertoire in influenza A virus-infected C57BL/6J (B6) mice exhibits a preferred TCRV-region bias toward the TRBV29 gene segment and an optimal complementarity determining region (CDR3) beta-length of 6 aa. Despite these restrictions, D(b)PA(224)-specific BV29(+) T cells use a wide array of unique CDR3beta sequences. Structural characterization of a single, TRBV29(+)D(b)P(A224)-specific TCRalphabeta-pMHCI complex demonstrated that CDR3alpha amino acid side chains made specific peptide interactions, but the CDR3beta main chain exclusively contacted peptides. Thus, length but not amino acid sequence was key for recognition and flexibility in Vbeta-region use. In support of this hypothesis, retrovirus expression of the D(b)PA(224)-specific TCRValpha-chain was used to constrain pairing within a naive/immune epitope-specific repertoire. The retrogenic TCRValpha paired with a diversity of CDR3betas in the context of a preferred TCRVbeta spectrum. Overall, these data provide an explanation for the combination of TCRV region bias and diversity within selected repertoires, even as they maintain exquisite pMHCI specificity.

UR - http://www.pnas.org/content/108/23/9536.full.pdf+html

U2 - 10.1073/pnas.1106851108

DO - 10.1073/pnas.1106851108

M3 - Article

VL - 108

SP - 9536

EP - 9541

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 23

ER -