|
|
|
|
|
|
|
||
T Cell Receptor Gene Rearrangement Lineage Analysis Reveals Clues for the Origin of Highly Restricted Antigen-specific Repertoires
2 Ludwig Institute for Cancer Research, Lausanne Branch, 1066 Epalinges, Switzerland
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: maryanski{at}cervi-lyon.inserm.fr
Due to ordered, stage-specific T cell receptor (TCR)-ß and -
locus gene rearrangements and cell division during T cell development, a given, ancestral TCR-ß locus VDJ rearrangement might be selected into the mature T cell repertoire as a small cohort of "half-sibling" progeny expressing identical TCR-ß chains paired with different TCR- chains. The low frequency of such a cohort relative to the total ß 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- chains selected to pair with ß chains encoded by an ancestral VDJ-ß rearrangement. If so, half-sibling T cells expressing structurally similar, but different TCR- 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-ß rearrangements but expressing different TCR- chains. The amplification of residual DJ-ß rearrangements as clonal markers allowed us to track T cells expressing different TCR- chains back to a common ancestral VDJ-ß rearrangement. Thus, the diversity of TCR-'s selected as partners for a given VDJ-ß rearrangement into the mature TCR repertoire may indeed be very limited.
Key Words: CD8+ T lymphocytes • antigen • receptors • sequence analysis • cell lineage
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
| TABLE OF CONTENTS |
|
