Fixing an irrelevant TCRα chain reveals the importance of TCRβ diversity for optimal TCRαβ pairing and function of virus-specific CD8+ T cells

Sophie Alessandra Valkenburg, E Bridie Day, Natasha G. Swan, Hayley A Croom, Francis R. Carbone, Peter C Doherty, Stephen J. Turner, Katherine Kedzierska

Research output: Contribution to journalArticleResearchpeer-review

Abstract

TCR repertoire diversity can influence the efficacy of CD8+ T-cell populations, with greater breadth eliciting better protection. We analyzed TCRβ diversity and functional capacity for influenza-specific CD8+ T cells expressing a single TCRα chain. Mice (A7) transgenic for the H2KbOVA257-264-specific Vα2.7 TCR were challenged with influenza to determine how fixing this "irrelevant" TCRα affects the "public" and restricted DbNP366 +CD8+ versus the "private" and diverse DbPA224 +CD8+ responses. Though both DbNP 366 +CD8+ and DbPA224 +CD8+ sets are generated in virus-primed A7 mice, the constrained DbNP366 +CD8+ population lacked the characteristic, public TCRVβ8.3, and consequently was reduced in magnitude and pMHC-I avidity. For the more diverse DbPA 224 +CD8+ T cells, this particular forcing led to a narrowing and higher TCRβ conservation of the dominant Vβ7, though the responses were of comparable magnitude to C57BL/6J controls. Interestingly, although both the TCRβ diversity and the cytokine profiles were reduced for the DbNP366 +CD8+ and DbPA224 +CD8+ sets in spleen, the latter measure of polyfunctionality was comparable for T cells recovered from the infected lungs of A7 and control mice. Even "sub-optimal" TCRαβ pairs can operate effectively when exposed in amilieu of high virus load. Thus, TCRβ diversity is important for optimal TCRαβ pairing and function when TCRα is limiting.

Original languageEnglish
Pages (from-to)2470-2481
Number of pages12
JournalEuropean Journal of Immunology
Volume40
Issue number9
DOIs
Publication statusPublished - Sep 2010
Externally publishedYes

Keywords

  • CD8 T cells
  • Influenza
  • TCR repertoire
  • Viral infection

Cite this

Valkenburg, Sophie Alessandra ; Day, E Bridie ; Swan, Natasha G. ; Croom, Hayley A ; Carbone, Francis R. ; Doherty, Peter C ; Turner, Stephen J. ; Kedzierska, Katherine. / Fixing an irrelevant TCRα chain reveals the importance of TCRβ diversity for optimal TCRαβ pairing and function of virus-specific CD8+ T cells. In: European Journal of Immunology. 2010 ; Vol. 40, No. 9. pp. 2470-2481.
@article{5ffc6c69923142ec93a3696c4eeb0697,
title = "Fixing an irrelevant TCRα chain reveals the importance of TCRβ diversity for optimal TCRαβ pairing and function of virus-specific CD8+ T cells",
abstract = "TCR repertoire diversity can influence the efficacy of CD8+ T-cell populations, with greater breadth eliciting better protection. We analyzed TCRβ diversity and functional capacity for influenza-specific CD8+ T cells expressing a single TCRα chain. Mice (A7) transgenic for the H2KbOVA257-264-specific Vα2.7 TCR were challenged with influenza to determine how fixing this {"}irrelevant{"} TCRα affects the {"}public{"} and restricted DbNP366 +CD8+ versus the {"}private{"} and diverse DbPA224 +CD8+ responses. Though both DbNP 366 +CD8+ and DbPA224 +CD8+ sets are generated in virus-primed A7 mice, the constrained DbNP366 +CD8+ population lacked the characteristic, public TCRVβ8.3, and consequently was reduced in magnitude and pMHC-I avidity. For the more diverse DbPA 224 +CD8+ T cells, this particular forcing led to a narrowing and higher TCRβ conservation of the dominant Vβ7, though the responses were of comparable magnitude to C57BL/6J controls. Interestingly, although both the TCRβ diversity and the cytokine profiles were reduced for the DbNP366 +CD8+ and DbPA224 +CD8+ sets in spleen, the latter measure of polyfunctionality was comparable for T cells recovered from the infected lungs of A7 and control mice. Even {"}sub-optimal{"} TCRαβ pairs can operate effectively when exposed in amilieu of high virus load. Thus, TCRβ diversity is important for optimal TCRαβ pairing and function when TCRα is limiting.",
keywords = "CD8 T cells, Influenza, TCR repertoire, Viral infection",
author = "Valkenburg, {Sophie Alessandra} and Day, {E Bridie} and Swan, {Natasha G.} and Croom, {Hayley A} and Carbone, {Francis R.} and Doherty, {Peter C} and Turner, {Stephen J.} and Katherine Kedzierska",
year = "2010",
month = "9",
doi = "10.1002/eji.201040473",
language = "English",
volume = "40",
pages = "2470--2481",
journal = "European Journal of Immunology",
issn = "0014-2980",
publisher = "Wiley-VCH Verlag GmbH & Co. KGaA",
number = "9",

}

Fixing an irrelevant TCRα chain reveals the importance of TCRβ diversity for optimal TCRαβ pairing and function of virus-specific CD8+ T cells. / Valkenburg, Sophie Alessandra; Day, E Bridie; Swan, Natasha G.; Croom, Hayley A; Carbone, Francis R.; Doherty, Peter C; Turner, Stephen J.; Kedzierska, Katherine.

In: European Journal of Immunology, Vol. 40, No. 9, 09.2010, p. 2470-2481.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Fixing an irrelevant TCRα chain reveals the importance of TCRβ diversity for optimal TCRαβ pairing and function of virus-specific CD8+ T cells

AU - Valkenburg, Sophie Alessandra

AU - Day, E Bridie

AU - Swan, Natasha G.

AU - Croom, Hayley A

AU - Carbone, Francis R.

AU - Doherty, Peter C

AU - Turner, Stephen J.

AU - Kedzierska, Katherine

PY - 2010/9

Y1 - 2010/9

N2 - TCR repertoire diversity can influence the efficacy of CD8+ T-cell populations, with greater breadth eliciting better protection. We analyzed TCRβ diversity and functional capacity for influenza-specific CD8+ T cells expressing a single TCRα chain. Mice (A7) transgenic for the H2KbOVA257-264-specific Vα2.7 TCR were challenged with influenza to determine how fixing this "irrelevant" TCRα affects the "public" and restricted DbNP366 +CD8+ versus the "private" and diverse DbPA224 +CD8+ responses. Though both DbNP 366 +CD8+ and DbPA224 +CD8+ sets are generated in virus-primed A7 mice, the constrained DbNP366 +CD8+ population lacked the characteristic, public TCRVβ8.3, and consequently was reduced in magnitude and pMHC-I avidity. For the more diverse DbPA 224 +CD8+ T cells, this particular forcing led to a narrowing and higher TCRβ conservation of the dominant Vβ7, though the responses were of comparable magnitude to C57BL/6J controls. Interestingly, although both the TCRβ diversity and the cytokine profiles were reduced for the DbNP366 +CD8+ and DbPA224 +CD8+ sets in spleen, the latter measure of polyfunctionality was comparable for T cells recovered from the infected lungs of A7 and control mice. Even "sub-optimal" TCRαβ pairs can operate effectively when exposed in amilieu of high virus load. Thus, TCRβ diversity is important for optimal TCRαβ pairing and function when TCRα is limiting.

AB - TCR repertoire diversity can influence the efficacy of CD8+ T-cell populations, with greater breadth eliciting better protection. We analyzed TCRβ diversity and functional capacity for influenza-specific CD8+ T cells expressing a single TCRα chain. Mice (A7) transgenic for the H2KbOVA257-264-specific Vα2.7 TCR were challenged with influenza to determine how fixing this "irrelevant" TCRα affects the "public" and restricted DbNP366 +CD8+ versus the "private" and diverse DbPA224 +CD8+ responses. Though both DbNP 366 +CD8+ and DbPA224 +CD8+ sets are generated in virus-primed A7 mice, the constrained DbNP366 +CD8+ population lacked the characteristic, public TCRVβ8.3, and consequently was reduced in magnitude and pMHC-I avidity. For the more diverse DbPA 224 +CD8+ T cells, this particular forcing led to a narrowing and higher TCRβ conservation of the dominant Vβ7, though the responses were of comparable magnitude to C57BL/6J controls. Interestingly, although both the TCRβ diversity and the cytokine profiles were reduced for the DbNP366 +CD8+ and DbPA224 +CD8+ sets in spleen, the latter measure of polyfunctionality was comparable for T cells recovered from the infected lungs of A7 and control mice. Even "sub-optimal" TCRαβ pairs can operate effectively when exposed in amilieu of high virus load. Thus, TCRβ diversity is important for optimal TCRαβ pairing and function when TCRα is limiting.

KW - CD8 T cells

KW - Influenza

KW - TCR repertoire

KW - Viral infection

UR - http://www.scopus.com/inward/record.url?scp=77956471264&partnerID=8YFLogxK

U2 - 10.1002/eji.201040473

DO - 10.1002/eji.201040473

M3 - Article

VL - 40

SP - 2470

EP - 2481

JO - European Journal of Immunology

JF - European Journal of Immunology

SN - 0014-2980

IS - 9

ER -