Evolution of the T cell repertoire during primary, memory, and recall responses to viral infection

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 prot eins. Following clearance of the infection, >90% of activated CD8(+) T cell s die, leaving behind a stable pool of memory CD8(+) T cells capable of res ponding to subsequent infections with enhanced kinetics. To probe the mecha nisms involved in the generation of T cell memory, we compared primary, mem ory, and secondary challenge virus-specific T cell repertoires using a comb ination of costaining with MHC class I tetramers and a panel of anti-V beta Abs, as well as complementarity-determining region 3 length distribution a nalysis of TCR V beta transcripts from cells sorted according to tetramer b inding. Following individual mice over time, we found identity between prim ary effector and memory TCR repertoires for each of three immunodominant ep itopes from lymphocytic choriomeningitis virus. During secondary responses, we found quantitative changes in epitope-specific T cell hierarchies but l ittle evidence for changes in V beta usage or complementarity-determining r egion 3 length distributions within epitope-specific populations. We conclu de that 1) selection of memory T cell populations is stochastic and not det ermined 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 r elative magnitudes of epitope-specific responses but does not significantly modify the repertoire of T cells responding to a given epitope.