Due to ordered, stage-specific T cell receptor (TCR)-β and -α locus gene rearrangements and cell division during T cell development, a given, ancestral TCR-β locus VDJ rearrangement might be selected into the mature T cell repertoire as a small cohort of “half-sibling” progeny expressing identical TCR-β chains paired with different TCR-α chains. The low frequency of such a cohort relative to the total αβ TCR repertoire precludes their direct identification and characterization in normal mice. We considered it possible that positive selection constraints might limit the diversity of TCR-α chains selected to pair with β chains encoded by an ancestral VDJ-β rearrangement. If so, half-sibling T cells expressing structurally similar, but different TCR-α chains might recognize the same foreign antigen. By single cell polymerase chain reaction analysis of antigen-specific TCRs selected during a model anti-tumor response, we were able to identify clusters of T cells sharing identical VDJ-β rearrangements but expressing different TCR-α chains. The amplification of residual DJ-β rearrangements as clonal markers allowed us to track T cells expressing different TCR-α chains back to a common ancestral VDJ-β rearrangement. Thus, the diversity of TCR-α's selected as partners for a given VDJ-β rearrangement into the mature TCR repertoire may indeed be very limited.
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3 March 2003
Article|
February 24 2003
T Cell Receptor Gene Rearrangement Lineage Analysis Reveals Clues for the Origin of Highly Restricted Antigen-specific Repertoires
Abdelbasset Hamrouni,
Abdelbasset Hamrouni
1INSERM U503, Centre d'Etudes et de Recherches en Virologie et Immunologie (CERVI), 69007 Lyon, France
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Anne Aublin,
Anne Aublin
1INSERM U503, Centre d'Etudes et de Recherches en Virologie et Immunologie (CERVI), 69007 Lyon, France
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Philippe Guillaume,
Philippe Guillaume
2Ludwig Institute for Cancer Research, Lausanne Branch, 1066 Epalinges, Switzerland
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Janet L. Maryanski
Janet L. Maryanski
1INSERM U503, Centre d'Etudes et de Recherches en Virologie et Immunologie (CERVI), 69007 Lyon, France
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Abdelbasset Hamrouni
1INSERM U503, Centre d'Etudes et de Recherches en Virologie et Immunologie (CERVI), 69007 Lyon, France
Anne Aublin
1INSERM U503, Centre d'Etudes et de Recherches en Virologie et Immunologie (CERVI), 69007 Lyon, France
Philippe Guillaume
2Ludwig Institute for Cancer Research, Lausanne Branch, 1066 Epalinges, Switzerland
Janet L. Maryanski
1INSERM U503, Centre d'Etudes et de Recherches en Virologie et Immunologie (CERVI), 69007 Lyon, France
Address correspondence to Janet L. Maryanski, INSERM U503, CERVI, 21 Avenue Tony Garnier, 69365 Lyon Cedex 07, France. Phone: 33-4-3728-2352; Fax: 33-4-3728-2341; E-mail: [email protected]
The online version of this article contains supplemental material.
*
Abbreviations used in this paper: aa, amino acid; DP, double positive; GL, germline; pMHC, MHC class I peptide; Tg, transgenic.
Received:
November 08 2002
Revision Received:
January 08 2003
Accepted:
January 08 2003
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2003
J Exp Med (2003) 197 (5): 601–614.
Article history
Received:
November 08 2002
Revision Received:
January 08 2003
Accepted:
January 08 2003
Citation
Abdelbasset Hamrouni, Anne Aublin, Philippe Guillaume, Janet L. Maryanski; T Cell Receptor Gene Rearrangement Lineage Analysis Reveals Clues for the Origin of Highly Restricted Antigen-specific Repertoires . J Exp Med 3 March 2003; 197 (5): 601–614. doi: https://doi.org/10.1084/jem.20021945
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