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Public T cell receptor beta-chains are not advantaged during positive selection

  • Anna Furmanski
    ,
  • Cristina Ferreira
    ,
  • Istvan Bartok
    ,
  • Sofia Dimakou
    ,
  • Jason Rice
    ,
  • Freda Stevenson
  • Imperial College Healthcare NHS Trust
    ,
  • University of Southampton
Research Output: Contribution to journal Article Peer-review

Abstract

Studies of human and murine T cells have shown that public TCR beta-chain rearrangements can dominate the Ag-specific and naive repertoires of distinct individuals. We show that mouse T cells responding to the minor histocompatibility Ag HYDbSmcy share an invariant Vbeta8.2-Jbeta2.3 TCR gene rearrangement. The dominance of this rearrangement shows that it successfully negotiated thymic selection and was highly favored during clonal expansion in all animals examined. We hypothesized that such beta-chains are advantaged during thymic and/or peripheral selection and, as a result, may be over-represented in the naive repertoire. A sequencing study was undertaken to examine the diversity of Vbeta8.2-Jbeta2.3 CDR3 loops from naive T cell repertoires of multiple mice. Public TCR beta-chain sequences were identified across different repertoires and MHC haplotypes. To determine whether such public beta-chains are advantaged during thymic selection, individual chains were followed through T cell development in a series of novel bone marrow competition chimeras. We demonstrate that beta-chains were positively selected with similar efficiency regardless of CDR3 loop sequence. Therefore, the establishment and maintenance of public beta-chains in the periphery is predominantly controlled by post-thymic events through modification of the primary, thymus-derived TCR repertoire.

Publication Information

Output type

Research Output: Contribution to journal Article Peer-review

Original language

English

Pages from-to (Number of pages)

Pages 1029-1039

Journal (Volume, Issue Number)

Journal of Immunology (Volume 180, Issue 2)

Publication milestones

  • Accepted/In press - 29/10/2007
  • Published - 04/01/2008

Publication status

Published - 04/01/2008

ISSN

0022-1767

External Publication IDs

  • handle.net: 10547/623406
  • Scopus: 40449142562

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