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Article

The CMV-Specific CD8+ T Cell Response Is Dominated by Supra-Public Clonotypes with High Generation Probabilities

1
Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München (TUM), 81675 Munich, Germany
2
German Center for Infection Research (DZIF), partner site Munich, Munich, Germany
3
ENPICOM B.V., 5211 AX ‘s-Hertogenbosch, The Netherlands
*
Authors to whom correspondence should be addressed.
Pathogens 2020, 9(8), 650; https://doi.org/10.3390/pathogens9080650
Received: 31 May 2020 / Revised: 1 July 2020 / Accepted: 11 August 2020 / Published: 13 August 2020
(This article belongs to the Special Issue Cytomegalovirus (CMV) Infection and Latency)
Evolutionary processes govern the selection of T cell clonotypes that are optimally suited to mediate efficient antigen-specific immune responses against pathogens and tumors. While the theoretical diversity of T cell receptor (TCR) sequences is vast, the antigen-specific TCR repertoire is restricted by its peptide epitope and the presenting major histocompatibility complex (pMHC). It remains unclear how many TCR sequences are recruited into an antigen-specific T cell response, both within and across different organisms, and which factors shape both of these distributions. Infection of mice with ovalbumin-expressing cytomegalovirus (IE2-OVA-mCMV) represents a well-studied model system to investigate T cell responses given their size and longevity. Here we investigated > 180,000 H2kb/SIINFEKL-recognizing TCR CDR3α or CDR3β sequences from 25 individual mice spanning seven different time points during acute infection and memory inflation. In-depth repertoire analysis revealed that from a pool of highly diverse, but overall limited sequences, T cell responses were dominated by public clonotypes, partly with unexpectedly extreme degrees of sharedness between individual mice (“supra-public clonotypes”). Public clonotypes were found exclusively in a fraction of TCRs with a high generation probability. Generation probability and degree of sharedness select for highly functional TCRs, possibly mediated through elevating intraindividual precursor frequencies of clonotypes. View Full-Text
Keywords: memory inflation; public clonotypes; generation probability; T cell response; TCR; convergent recombination; TCR repertoire memory inflation; public clonotypes; generation probability; T cell response; TCR; convergent recombination; TCR repertoire
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MDPI and ACS Style

Schober, K.; Fuchs, P.; Mir, J.; Hammel, M.; Fanchi, L.; Flossdorf, M.; Busch, D.H. The CMV-Specific CD8+ T Cell Response Is Dominated by Supra-Public Clonotypes with High Generation Probabilities. Pathogens 2020, 9, 650. https://doi.org/10.3390/pathogens9080650

AMA Style

Schober K, Fuchs P, Mir J, Hammel M, Fanchi L, Flossdorf M, Busch DH. The CMV-Specific CD8+ T Cell Response Is Dominated by Supra-Public Clonotypes with High Generation Probabilities. Pathogens. 2020; 9(8):650. https://doi.org/10.3390/pathogens9080650

Chicago/Turabian Style

Schober, Kilian, Pim Fuchs, Jonas Mir, Monika Hammel, Lorenzo Fanchi, Michael Flossdorf, and Dirk H. Busch 2020. "The CMV-Specific CD8+ T Cell Response Is Dominated by Supra-Public Clonotypes with High Generation Probabilities" Pathogens 9, no. 8: 650. https://doi.org/10.3390/pathogens9080650

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