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Estimating the Precursor Frequency of Naive Antigen-specific CD8 T Cells
Open accessAbstract
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.
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Cites
Phenotypic Analysis of Antigen-Specific T Lymphocytes
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MethodSelf-citationA Direct Estimate of the Human αβ T Cell Receptor Diversity
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Self-citationDefective CD8 T Cell Memory Following Acute Infection Without CD4 T Cell Help
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Self-citationEffector CD8 T cells dedifferentiate into long-lived memory cells
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Self-citationEndogenous naive CD8+ T cell precursor frequency regulates primary and memory responses to infection
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How many TCR clonotypes does a body maintain?
Lythe, G., Callard, R. E., Hoare, R. L., & Molina-París, C. (2016) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2015.10.016 · Cited by 175
“(Langman and Cohn, 1987; Blattman et al., 2002; Ciupe et al., 2013; Thomas et al., 2014).”
Armed and Ready: Transcriptional Regulation of Tissue-Resident Memory CD8 T Cells
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Self-citationAcquired transcriptional programming in functional and exhausted virus-specific CD8 T cells.
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Self-citationBehr, F. M., Beumer‐Chuwonpad, A., Kragten, N. A. M., Wesselink, T. H., Stark, R., & van Gisbergen, K. P. J. M. (2021) · European Journal of Immunology · doi:10.1002/eji.202048737 · Cited by 30
Metadata
- Authors
- Blattman, J. N., Antia, R., Sourdive, D. J. D., Wang, X., Kaech, S. M., Murali-Krishna, K., Altman, J. D., & Ahmed, R.
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2002-03-04
- Volume
- 195
- Issue
- 5
- Pages
- 657-664
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2110459643
- Cited by
- 583
- References
- 2
- FWCI
- 9.84
- Type
- journal article
- Language
- en
- Open access
- bronze
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