International Immunology Advance Access originally published online on June 21, 2005
International Immunology 2005 17(7):931-941; doi:10.1093/intimm/dxh273
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Delayed expansion of a restricted T cell repertoire by low-density TCR ligands
1 Laboratoire d'Immunologie, Centre de recherche du Centre Hospitalier de l'Université de Montréal, Hôpital Saint-Luc, Montréal, Québec H2X 1P1, Canada
2 Faculty of Medicine, Division of Experimental Medicine, McGill University, Montréal, Québec H3A 1A3, Canada
3 Département de Microbiologie et Immunologie, Université de Montréal, Montréal, Québec H3C 3J7, Canada
4 Department of Microbiology and Immunology, McGill University, Montréal, Québec H3A 2B4, Canada
Correspondence to: R.-P. Sékaly; E-mail: rafick-pierre.sekaly{at}umontreal.ca
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 TCRVß-bearing T cells, with the specific, non-stochastic exclusion of some TCRVß+ T cells from the activated pool. Our results suggest that the failure of these TCRVß-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 TCRVß-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.