Endogenous naive CD8+ T cell precursor frequency regulates primary and memory responses to infection

Obar, Joshua J.; Khanna, Kamal M.; Lefrançois, Leo

doi:10.1016/j.immuni.2008.04.010

Cited by 449T-cell and B-cell ImmunologyImmunotherapy and Immune ResponsesImmune responses and vaccinations

Endogenous naive CD8+ T cell precursor frequency regulates primary and memory responses to infection

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Obar, Joshua J., Khanna, Kamal M., Lefrançois, Leo·2008·Immunity

DOI 10.1016/j.immuni.2008.04.010PMC PMC2836785

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Abstract

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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Increased clonal sizes are a hallmark of immune memory, and clonal dominance is normal for memory T cell responses to a single peptide, likely due to antigen-driven selection.
“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 mice, the TCR repertoire to an antigenic peptide follows a power law distribution with many specificities and only a few gaining dominance.
“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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“Of note, the number of f-MIIINA:H2-M3-specific CD8 cells in naive mice is high compared to the average number of naive CD8 T cell precursors specific to foreign antigens presented by conventional MHCIa pathways ( 200 cells) (Obar et al., 2008).”
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Self-citation

Endogenous naive CD8 T cell precursor frequency and infection type control CD62L gene expression (85.6)
Obar, J. J., Khanna, K. M., Pham, Q.-M., & Lefrançois, L. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.supp.85.6
Self-citation
Estimating the Precursor Frequency of Naive Antigen-specific CD8 T Cells
Blattman, J. N., Antia, R., Sourdive, D. J. D., Wang, X., Kaech, S. M., Murali‐Krishna, K., Altman, J. D., & Ahmed, R. (2002) · The Journal of Experimental Medicine · doi:10.1084/jem.20001021 · Cited by 583 · see citing works
High Frequencies of Virus-Specific CD8 + T-Cell Precursors
Seedhom, M. O., Jellison, E. R., Daniels, K. A., & Welsh, R. M. (2009) · Journal of Virology · doi:10.1128/jvi.01722-09 · Cited by 30 · see citing works
Initial T Cell Receptor Transgenic Cell Precursor Frequency Dictates Critical Aspects of the CD8+ T Cell Response to Infection
Badovinac, V. P., Haring, J. S., & Harty, J. T. (2007) · Immunity · doi:10.1016/j.immuni.2007.04.013 · Cited by 406 · see citing works
Primary CTL response magnitude in mice is determined by the extent of naive T cell recruitment and subsequent clonal expansion
Gruta, N. L. L., Rothwell, W. T., Cukalac, T., Swan, N. G., Valkenburg, S. A., Kedzierska, K., Thomas, P. G., Doherty, P. C., & Turner, S. J. (2010) · Journal of Clinical Investigation · doi:10.1172/jci41538 · Cited by 166 · see citing works

Authors: Obar, J. J., Khanna, K. M., & Lefrançois, L.
Affiliations: UConn Health (US)
Corresponding author: Lefrançois, Leo
ORCID: Obar, Joshua J.
Khanna, Kamal M.
Venue: Immunity
Publisher: Elsevier BV
Published: 2008-06
Volume: 28
Issue: 6
Pages: 859-869
ISSN: 1074-7613 (ISSN-L)
DOI: 10.1016/j.immuni.2008.04.010
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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Endogenous naive CD8+ T cell precursor frequency regulates primary and memory responses to infection

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