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Endogenous Naive CD8+ T Cell Precursor Frequency Regulates Primary and Memory Responses to Infection
Open accessAbstract
Through genetic recombination, the adaptive immune system generates a diverse T cell repertoire allowing recognition of a vast spectrum of foreign antigens. Any given CD8+ T cell specificity is thought to be rare, but none have been directly quantified. Here, major histocompatibility complex tetramer and magnetic-bead technology were coupled to quantitate naive antigen-specific CD8+ T cells and the early response to infection. Among six specificities measured, the number of naive antigen-specific precursors ranged from approximately 80 to 1200 cells/mouse. After vesicular stomatitis virus infection, the antigen-specific CD8+ T cell response occurred in discrete phases: prolonged activation of a subset of cells over the first 72 hr followed by a rapid proliferative burst. Naive precursor frequency altered response kinetics and regulated immunodominance, as well as the time required for the responding population to shift toward CD62L(hi) memory cells. Thus, initial endogenous precursor frequencies were surprisingly diverse and not only regulated initial immune response characteristics but also controlled memory CD8+ T cell lineage decisions.
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“Increase in clonal sizes is a hallmark of immune memory; moreover, clonal dominance is quite normal for the memory T cell repertoire responding to a single peptide”
From Successful and Maladaptive T Cell Aging (2017) · cites this paper as Obar et al., 2008
In the citing paper
“In mice, the TCR repertoire to an antigenic peptide follows a power law distribution involving a large number of T cell specificities, with only a few of them gaining dominance”
From Successful and Maladaptive T Cell Aging (2017) · cites this paper as Obar et al., 2008
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Becattini, S. (2014) · Repository for Publications and Research Data (ETH Zurich) · doi:10.3929/ethz-a-010271553
The Role of CD4+ T cells in the CD8+ T cell Response to Vaccinia Viral Infection
Novy, P. (2010) · DukeSpace (Duke University)
Best, J. A., Blair, D. A., Knell, J., Yang, E., Mayya, V., Doedens, A. L., Dustin, M. L., Goldrath, A. W., Monach, P. A., Shinton, S. A., et al. (2013) · PMC
Strategies to improve gene expression and targeting for DNA vaccine development
Skinner, N. (2013) · University of Minnesota Digital Conservancy (University of Minnesota)
Metadata
- Authors
- Obar, J. J., Khanna, K. M., & Lefrançois, L.
- Affiliations
- UConn Health (US)
- Corresponding author
- Lefrançois, Leo
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2008-06
- Volume
- 28
- Issue
- 6
- Pages
- 859-869
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC2836785
- OpenAlex
- W2027434623
- Cited by
- 449
- References
- 62
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 7 · 2023: 19 · 2022: 14 · 2021: 18 · 2020: 20 · 2019: 13 · 2018: 21 · 2017: 14 · 2016: 17 · 2015: 29 · 2014: 36 · 2013: 57 · 2012: 51
- FWCI
- 15.50
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1872 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (AI41576, F32AI074277)
- Damon Runyon Cancer Research Foundation (DRG-1886-05)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- naive CD8+ T cells, T cell precursor frequency, antigen-specific T cells, primary immune response, memory T cells, immunodominance, L-selectin, T cell proliferation, MHC tetramers, magnetic bead separation
- MeSH terms
- Animals, Immunologic Memory, Lymphocyte Activation, Mice, Inbred C57BL, Mice, Transgenic, RNA, Messenger, Vesicular stomatitis Indiana virus, Histocompatibility Antigens Class I, Rhabdoviridae Infections, CD8-Positive T-Lymphocytes, Lymphocyte Count, L-Selectin, Cell Proliferation, Mice, Precursor Cells, T-Lymphoid
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