Evolution of the T Cell Repertoire During Primary, Memory, and Recall Responses to Viral Infection

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Abstract
Many viral infections induce a broad repertoire of CD8+ T cell responses that initiate recognition and elimination of infected cells by interaction of TCRs with viral peptides presented on infected cells by MHC class I proteins. Following clearance of the infection, >90% of activated CD8+ T cells die, leaving behind a stable pool of memory CD8+ T cells capable of responding to subsequent infections with enhanced kinetics. To probe the mechanisms involved in the generation of T cell memory, we compared primary, memory, and secondary challenge virus-specific T cell repertoires using a combination of costaining with MHC class I tetramers and a panel of anti-Vβ Abs, as well as complementarity-determining region 3 length distribution analysis of TCR Vβ transcripts from cells sorted according to tetramer binding. Following individual mice over time, we found identity between primary effector and memory TCR repertoires for each of three immunodominant epitopes from lymphocytic choriomeningitis virus. During secondary responses, we found quantitative changes in epitope-specific T cell hierarchies but little evidence for changes in Vβ usage or complementarity-determining region 3 length distributions within epitope-specific populations. We conclude that 1) selection of memory T cell populations is stochastic and not determined by a distinct step of clonal selection necessary for survival from the acute responding population, and 2) maturation of the T cell repertoire during secondary lymphocytic choriomeningitis virus infection alters the relative magnitudes of epitope-specific responses but does not significantly modify the repertoire of T cells responding to a given epitope.