T cell receptor clonotype influences epitope hierarchy in the CD8+T cell response to respiratory syncytial virus infection

Padma Billam, Kathryn L. Bonaparte, Jie Liu, Tracy J. Ruckwardt, Man Chen, Alex Ryder, Rui Wang, Pradyot Dash, Paul G. Thomas, Barney S. Graham

Research output: Contribution to journalArticle

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Abstract

CD8+ T cell responses are important for recognizing and resolving viral infections. To better understand the selection and hierarchy of virus-specific T cell responses, we compared the T cell receptor (TCR) clonotype in parent and hybrid strains of respiratory syncytial virus-infected mice. K d M2 82-90 (SYIGSINNI) in BALB/c and D b M 187-195 (NAITNAKII) in C57Bl/6 are both dominant epitopes in parent strains but assume a distinct hierarchy, with K d M2 82-90 dominant to D b M 187-195 in hybrid CB6F1/J mice. The dominant K d M2 82-90 response is relatively public and is restricted primarily to the highly prevalent Vβ13.2 in BALB/c and hybrid mice, whereas D b M 187-195 responses in C57BL/6 mice are relatively private and involve multiple Vβ subtypes, some of which are lost in hybrids. A significant frequency of TCR CDR3 sequences in the D b M 187-195 response have a distinct "(D/E)WG" motif formed by a limited number of recombination strategies. Modeling of the dominant epitope suggested a flat, featureless structure, but D b M 187-195 showed a distinctive structure formed by Lys 7 . The data suggest that common recombination events in prevalent Vβ genes may provide a numerical advantage in the T cell response and that distinct epitope structures may impose more limited options for successful TCR selection. Defining how epitope structure is interpreted to inform T cell function will improve the design of future gene-based vaccines.

Original languageEnglish (US)
Pages (from-to)4829-4841
Number of pages13
JournalJournal of Biological Chemistry
Volume286
Issue number6
DOIs
StatePublished - Feb 11 2011

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Respiratory Syncytial Virus Infections
T-cells
T-Cell Antigen Receptor
Viruses
Epitopes
T-Lymphocytes
Genetic Recombination
Genes
Respiratory Syncytial Viruses
Virus Diseases
Inbred C57BL Mouse
Vaccines

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

T cell receptor clonotype influences epitope hierarchy in the CD8+T cell response to respiratory syncytial virus infection. / Billam, Padma; Bonaparte, Kathryn L.; Liu, Jie; Ruckwardt, Tracy J.; Chen, Man; Ryder, Alex; Wang, Rui; Dash, Pradyot; Thomas, Paul G.; Graham, Barney S.

In: Journal of Biological Chemistry, Vol. 286, No. 6, 11.02.2011, p. 4829-4841.

Research output: Contribution to journalArticle

Billam, P, Bonaparte, KL, Liu, J, Ruckwardt, TJ, Chen, M, Ryder, A, Wang, R, Dash, P, Thomas, PG & Graham, BS 2011, 'T cell receptor clonotype influences epitope hierarchy in the CD8+T cell response to respiratory syncytial virus infection', Journal of Biological Chemistry, vol. 286, no. 6, pp. 4829-4841. https://doi.org/10.1074/jbc.M110.191437
Billam, Padma ; Bonaparte, Kathryn L. ; Liu, Jie ; Ruckwardt, Tracy J. ; Chen, Man ; Ryder, Alex ; Wang, Rui ; Dash, Pradyot ; Thomas, Paul G. ; Graham, Barney S. / T cell receptor clonotype influences epitope hierarchy in the CD8+T cell response to respiratory syncytial virus infection. In: Journal of Biological Chemistry. 2011 ; Vol. 286, No. 6. pp. 4829-4841.
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