Estimating the Precursor Frequency of Naive Antigen-specific CD8 T Cells

By J. Blattman, R. Antia, D. Sourdive, Xiaochi Wang, S. Kaech, Kaja Murali-Krishna, J. Altman, Rafi Ahmed. Journal of Experimental Medicine, 2002

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The constraint of fitting a diverse repertoire of antigen specificities in a limited total population of lymphocytes results in the frequency of naive cells specific for any given antigen (defined as the precursor frequency) being below the limit of detection by direct measurement. We have estimated this precursor frequency by titrating a known quantity of antigen-specific cells into naive recipients. Adoptive transfer of naive antigen-specific T cell receptor transgenic cells into syngeneic nontransgenic recipients, followed by stimulation with specific antigen, results in activation and expansion of both donor and endogenous antigen-specific cells in a dose-dependent manner. The precursor frequency is equal to the number of transferred cells when the transgenic and endogenous responses are of equal magnitude. Using this method we have estimated the precursor frequency of naive CD8 T cells specific for the H-2Db–restricted GP33–41 epitope of LCMV to be 1 in 2 × 105. Thus, in an uninfected mouse containing ∼2-4 × 107 naive CD8 T cells we estimate there to be 100–200 epitope-specific cells. After LCMV infection these 100–200 GP33-specific naive CD8 T cells divide >14 times in 1 wk to reach a total of ∼107 cells. Approximately 5% of these activated GP33-specific effector CD8 T cells survive to generate a memory pool consisting of ∼5 × 105 cells. Thus, an acute LCMV infection results in a >1,000-fold increase in precursor frequency of DbGP33-specific CD8 T cells from 2 × 102 naive cells in uninfected mice to 5 × 105 memory cells in immunized mice.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/5edbac9eafa3ba5dd518a4faa840597b7327f79c

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Citations in the corpus

Immunological mechanisms of vaccination (2011, background): “Thus, in an uninfected mouse containing ∼2 × 10 7 to 4 × 10 7 naive CD8 + T cells, there are estimated to be 100–1,200 epitope-specific cell”
Chapter 1. General introduction (2015, positive): “Binding of retinoic acid to CRABP1 induces degradation of retinoic acid into inactive metabolites (4).”
Properties of MHC Class I Presented Peptides That Enhance Immunogenicity (2013, background): “A specific pMHC will be recognized by an estimated average of one in 100,000 naive T-cells [1–4], but this precursor frequency”
Heterologous immunity provides a potent barrier to transplantation tolerance. (2003, background): “Although the frequency of naive T cells available to respond to any given pathogen is relatively small (approximately 1:200,000), the proportion that can directly recognize foreign MHC represents a substantial fraction of the total T cell repertoire (up to 1–10%) (6, 7).”
Interleukin 15 Is Required for Proliferative Renewal of Virus-specific Memory CD8 T Cells (2002, background): “For example, after infection of mice with lymphocytic choriomeningitis virus (LCMV) * there is up to a 1,000-fold increase in the precursor frequency of virus-specific CD8 T cells (7, 8 ). Substantial increases (200‐500fold) in the numbers of antigen-specific CD8 T cells are also seen after clearan”
Memory CD8 T-Cell Differentiation during Viral Infection (2004, background): “CD8 T-cell response to infection, this population, which corresponds to 10(2) cells/spleen in the mouse, can expand to greater than 10(7) cells/spleen (17, 85).”
The many important facets of T-cell repertoire diversity (2004, background): “Numbers of naive CTL precursors were recently estimated at 100–200 by two groups investigating two different responses — LCMV-derived gp33 peptide bound to H–2D b (LCMV gp33/H–2D b”
T Cell Factor 1-Expressing Memory-like CD8(+) T Cells Sustain the Immune Response to Chronic Viral Infections. (2016, background): “The fold expansion of P14 T-cells in secondary hosts was determined relative to an estimated 10% “take” of transferred input cells (Blattman et al., 2002).”
Naive CD4(+) T cell frequency varies for different epitopes and predicts repertoire diversity and response magnitude. (2007, methodology): “N IH -PA Author M anuscript N IH -PA Author M anuscript N IH -PA Author M anuscript on the epitope in question (Blattman et al., 2002; Butz and Bevan, 1998; McHeyzer-Williams and Davis, 1995; Stetson et al., 2002; Whitmire et al., 2006).”