TY - JOUR
T1 - Evolution of the T cell repertoire during primary, memory, and recall responses to viral infection
AU - Blattman, J. N.
AU - Sourdive, D. J.D.
AU - Murali-Krishna, K.
AU - Ahmed, R.
AU - Altman, J. D.
PY - 2000/12/1
Y1 - 2000/12/1
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.165.11.6081
DO - 10.4049/jimmunol.165.11.6081
M3 - Article
C2 - 11086040
AN - SCOPUS:0034547839
SN - 0022-1767
VL - 165
SP - 6081
EP - 6090
JO - Journal of Immunology
JF - Journal of Immunology
IS - 11
ER -