Immunity to a number of viruses is known to be mediated by T cells, implying that many vaccines should be engineered to elicit strong T cell memory. While the phenomenon of functional T cell memory may be accounted for by increased frequencies of antigen specific cells with possibly heightened sensitivity, many of the mechanistic details of memory T cell development and maintenance remain unresolved. Precise analysis of memory T cells has been hampered by the absence of methods for detecting and purifying low frequency populations of antigen-specific T cells without resort to in vitro culture techniques. Recently described soluble tetramers of peptide-bound MHC complexes that label T cells according to the specificity of their antigen receptor provide a general solution to the problem. This technique will be applied to answer two specific questions on the nature of T cell memory, using well characterized CD8+ T cell responses to LCMV. 1) What is the lifespan of memory T cells? The MHC tetramers will provide definitive answers to this question through analysis of extremely pure populations of memory T cells (possessing several distinct antigen-specificities) generated during the course of physiologically relevant responses. As a corollary to the lifespan studies, the stability of the expression patterns of a large number of cell adhesion molecules, signaling molecules, and homing receptors will be analyzed on multiple antigen-specific populations within the same mouse. 2) Is the development of memory T cells dependent upon a distinct clonal selection step? If so, there will be detectable differences in the distribution of functional clonotypic T cell receptor (TCR) genes expressed by T cells involved in the primary response and those which form the memory compartment. These populations will be sorted using appropriate MHC tetramers. Pools of sorted cells specific for a single antigen will be analyzed by TCR spectratyping; sequences of functional TCR genes from single sorted cells will be analyzed using highly optimized RT-PCR techniques.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI042373-01
Application #
2464631
Study Section
Experimental Virology Study Section (EVR)
Project Start
1997-12-01
Project End
2001-11-30
Budget Start
1997-12-01
Budget End
1998-11-30
Support Year
1
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Emory University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
042250712
City
Atlanta
State
GA
Country
United States
Zip Code
30322
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Romagnoli, Pablo A; Premenko-Lanier, Mary F; Loria, Gilbert D et al. (2013) CD8 T cell memory recall is enhanced by novel direct interactions with CD4 T cells enabled by MHC class II transferred from APCs. PLoS One 8:e56999
Miller, Joseph D; Peters, Michael; Oran, Alp E et al. (2002) CD94/NKG2 expression does not inhibit cytotoxic function of lymphocytic choriomeningitis virus-specific CD8+ T cells. J Immunol 169:693-701
Vance, R E; Kraft, J R; Altman, J D et al. (1998) Mouse CD94/NKG2A is a natural killer cell receptor for the nonclassical major histocompatibility complex (MHC) class I molecule Qa-1(b). J Exp Med 188:1841-8