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International Immunology Advance Access published online on June 21, 2005
International Immunology, doi:10.1093/intimm/dxh273
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© The Japanese Society for Immunology. 2005. All rights reserved. For permissions, please e-mail: journals.permissions@oupjournals.org
Received December 20, 2004
Accepted April 25, 2005

Article

Delayed expansion of a restricted T cell repertoire by low-density TCR ligands

Pascal M. Lavoie 1 *, Alain R. Dumont 1 *, Helen McGrath 2, Anne-Elen Kernaleguen 3, and Rafick-P. Sékaly 4*

1 Laboratoire d'Immunologie, Centre de recherche du Centre Hospitalier de l'Université de Montréal, Hôpital Saint-Luc, Montréal, Québec H2X 1P1, Canada; Faculty of Medicine, Division of Experimental Medicine, McGill University, Montréal, Québec H3A 1A3, Canada
2 Laboratoire d'Immunologie, Centre de recherche du Centre Hospitalier de l'Université de Montréal, Hôpital Saint-Luc, Montréal, Québec H2X 1P1, Canada
3 Laboratoire d'Immunologie, Centre de recherche du Centre Hospitalier de l'Université de Montréal, Hôpital Saint-Luc, Montréal, Québec H2X 1P1, Canada; Département de Microbiologie et Immunologie, Université de Montréal, Montréal, Québec H3C 3J7, Canada
4 Laboratoire d'Immunologie, Centre de recherche du Centre Hospitalier de l'Université de Montréal, Hôpital Saint-Luc, Montréal, Québec H2X 1P1, Canada; Faculty of Medicine, Division of Experimental Medicine, McGill University, Montréal, Québec H3A 1A3, Canada; Département de Microbiologie et Immunologie, Université de Montréal, Montréal, Québec H3C 3J7, Canada; Department of Microbiology and Immunology, McGill University, Montréal, Québec H3A 2B4, Canada

* To whom correspondence should be addressed.
Rafick-P. Sékaly, E-mail: rafick-pierre.sekaly{at}umontreal.ca


  Abstract

The role of TCR ligand density (i.e. the number of antigen-MHC complexes) in modulating the diversity of a T cell response selected from a pool of naive precursors remains largely undefined. By measuring early-activation markers up-regulation and proliferation following stimulation with staphylococcal enterotoxin A (SEA), we demonstrate that decreasing the ligand dose below an optimal concentration leads to the delayed activation of a restricted set of TCRV{beta}-bearing T cells, with the specific, non-stochastic exclusion of some TCRV{beta}+ T cells from the activated pool. Our results suggest that the failure of these TCRV{beta}-bearing T cells to reach the activation threshold at sub-optimal ligand concentration is due to the inefficiency of TCR engagement, as measured by TCR internalization, and does not correlate with the relative precursor frequency in the non-immune repertoire. Moreover, even at SEA concentrations that lead to the simultaneous proliferation of all SEA-reactive T cells, we observe marked differences in the ability to secrete cytokines among the different responsive TCRV{beta}-bearing T cells. Altogether, our results indicate that the development of a T cell response to a scarce display of ligand significantly narrows TCR repertoire diversity by mechanisms that involve focusing of the repertoire on the expansion of those T cells with the highest avidity of TCR engagement.

Keywords: antigen presentation; avidity; immune response; staphylococcal enterotoxin A; T cell proliferation.

*These authors contributed equally to this work.


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