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Proc Natl Acad Sci U S A. 2003 Sep 16;100(19):11143-7. Epub 2003 Sep 3.

Population dynamics of rapid fixation in cytotoxic T lymphocyte escape mutants of influenza A.

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Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, United Kingdom.


The dynamics of cellular immunity against pathogens, and its interaction with the human MHC system, is a key area for empirical research, both within individual hosts and in population genetic surveys. However, in contrast with humoral immunity, the dynamics of cellular immunity have not been modeled at the population level. Here, we address this lacuna with a model of recently observed dramatic invasions of cytotoxic T lymphocyte escape mutants in human influenza A. In particular, we offer an explanation for the rapid fixation of a HLA-B27 restricted cytotoxic T lymphocyte escape mutant on the nucleoprotein that emerged in the 1993-1994 season. We find that the dynamics within a single season of influenza do not provide a realistic description, but a model of the full annual dynamics can offer a possible explanation. Our model is deterministic for the winter epidemic, and stochastic for the summer period. An escape mutant that leads to a slightly longer infection in a small proportion of hosts has a substantial advantage through summer persistence. Furthermore, if a small number of founding cases are responsible for initiating each epidemic, then this effect of rapid mutant fixation is amplified.

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