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Asynchronous Differentiation of CD8 T Cells That Recognize Dominant and Cryptic Antigens¹

Chantal Baron^*,, Marie-Christine Meunier^*,, Étienne Caron^*,, Caroline Côté^*,, Mark J. Cameron, David J. Kelvin, Richard LeBlanc, Vincent Rineau^*, and Claude Perreault^2,*,

^* Institute of Research in Immunology and Cancer, University of Montreal, Montreal, Quebec, Canada; Guy-Bernier Research Center, Maisonneuve-Rosemont Hospital, Montreal, Quebec, Canada; Toronto General Research Institute, Toronto, Ontario, Canada; and Centre Hospitalier Universitaire de Sherbrooke, Fleurimont, Quebec, Canada

Restriction of T cell responses to a few epitopes (immunodominance) is a central feature of immune responses. We analyzed the entire transcriptome of effector CD8 T cells specific for a dominant (H7^a) and a cryptic (HY) mouse Ag and performed a longitudinal analysis of selected T cell differentiation markers. We found that Ag specificity had a relatively modest influence on the repertoire of genes that are transcriptionally modulated by the CD8 T cell differentiation program. Although the differentiation programs of anti-H7^a and anti-HY T cells were similar, they did not progress simultaneously. The expansion peak of anti-H7^a T cells was reached on day 10 while that of anti-HY T cells was attained on days 15–20. Between days 10 and 20, anti-H7^a T cells were in the contraction phase and anti-HY T cells in the expansion phase. Furthermore, expansion and development of effector function were well-synchronized in anti-H7^a T cells but were disconnected in anti-HY T cells. We propose that, by leading to selective expansion of the fittest CD8 T cells, immunodominance may be beneficial to the host. Inhibition of the T cell response to cryptic Ag would ensure that host resources (APC, cytokines) for which T cells compete are devoted to T cells with the best effector potential. One implication is that favoring expansion of the fittest effector T cells in general may be more important than increasing the diversity of the T cell repertoire.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Grant 014271 (to C.P.) from the National Cancer Institute of Canada. M.-C.M. was supported by a training grant from the National Cancer Institute of Canada. C.P. holds a Canada Research Chair in Immunobiology.

² Address correspondence and reprint requests to Dr. Claude Perreault, Institute of Research in Immunology and Cancer, University of Montreal, Casier postal 6128 Succursale, Centreville, Montréal, Quebec, Canada H3C 3J7. E-mail address: c.perreault{at}videotron.ca

³ Abbreviations used in this paper: MiHA, minor histocompatibility Ag; qrt-PCR, quantitative real-time PCR; MFI, mean fluorescence intensity; Tet, tetramer.

⁴ The online version of this article contains supplemental material.