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*
Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322; and
Unite de Biologie Moleculaire du Gene Institut Pasteur, Paris, France
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-V
Abs, as well as complementarity-determining region 3
length distribution analysis of TCR V 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
V 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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B. A. Small, S. A. Dressel, C. W. Lawrence, D. R. Drake III, M. H. Stoler, R. I. Enelow, and T. J. Braciale CD8+ T Cell-mediated Injury In Vivo Progresses in the Absence of Effector T Cells J. Exp. Med., December 17, 2001; 194(12): 1835 - 1846. [Abstract] [Full Text] [PDF]
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 J. L. Matsuda, L. Gapin, N. Fazilleau, K. Warren, O. V. Naidenko, and M. Kronenberg Natural killer T cells reactive to a single glycolipid exhibit a highly diverse T cell receptor beta repertoire and small clone size PNAS, October 5, 2001; (2001) 221445298. [Abstract] [Full Text] [PDF]
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J. M. Grayson, J. G. Lanier, J. D. Altman, and R. Ahmed The Role of p53 in Regulating Antiviral T Cell Responses J. Immunol., August 1, 2001; 167(3): 1333 - 1337. [Abstract] [Full Text] [PDF]
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J. L. Matsuda, L. Gapin, N. Fazilleau, K. Warren, O. V. Naidenko, and M. Kronenberg Natural killer T cells reactive to a single glycolipid exhibit a highly diverse T cell receptor beta repertoire and small clone size PNAS, October 23, 2001; 98(22): 12636 - 12641. [Abstract] [Full Text] [PDF]
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A. D. Hislop, N. E. Annels, N. H. Gudgeon, A. M. Leese, and A. B. Rickinson Epitope-specific Evolution of Human CD8+ T Cell Responses from Primary to Persistent Phases of Epstein-Barr Virus Infection J. Exp. Med., April 1, 2002; 195(7): 893 - 905. [Abstract] [Full Text] [PDF]
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