Exploring the pre-immune landscape of antigen-specific T cells

Genome Medicine
Mikhail V PogorelyyMikhail Shugay

Abstract

Adaptive immune responses to newly encountered pathogens depend on the mobilization of antigen-specific clonotypes from a vastly diverse pool of naive T cells. Using recent advances in immune repertoire sequencing technologies, models of the immune receptor rearrangement process, and a database of annotated T cell receptor (TCR) sequences with known specificities, we explored the baseline frequencies of T cells specific for defined human leukocyte antigen (HLA) class I-restricted epitopes in healthy individuals. We used a database of TCR sequences with known antigen specificities and a probabilistic TCR rearrangement model to estimate the baseline frequencies of TCRs specific to distinct antigens epitopespecificT-cells. We verified our estimates using a publicly available collection of TCR repertoires from healthy individuals. We also interrogated a database of immunogenic and non-immunogenic peptides is used to link baseline T-cell frequencies with epitope immunogenicity. Our findings revealed a high degree of variability in the prevalence of T cells specific for different antigens that could be explained by the physicochemical properties of the corresponding HLA class I-bound peptides. The occurrence of certain rearrangements...Continue Reading

References

Mar 6, 2002·The Journal of Experimental Medicine·Joseph N BlattmanRafi Ahmed
Feb 28, 2008·Nature Reviews. Immunology·Vanessa VenturiMiles P Davenport
May 6, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·J Joseph MelenhorstA John Barrett
Sep 19, 2008·Journal of Virology·Anthony Tanoto TanAntonio Bertoletti
Nov 4, 2008·Nucleic Acids Research·Marie-Paule LefrancPatrice Duroux
Jul 17, 2009·The Journal of Biological Chemistry·David K ColeAndrew K Sewell
Apr 21, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Marc K Jenkins, James J Moon
Aug 25, 2012·Nature Reviews. Immunology·Andrew K Sewell
Sep 19, 2012·Proceedings of the National Academy of Sciences of the United States of America·Anand MuruganCurtis G Callan
Dec 21, 2012·Blood·Julia Ekeruche-MakindeLinda Wooldridge
Nov 10, 2013·PLoS Computational Biology·Jorg J A CalisBjoern Peters
Jan 9, 2014·Frontiers in Immunology·Mikhail ShugayDmitriy M Chudakov
Feb 20, 2014·Frontiers in Immunology·Andrew J Yates
Jun 20, 2014·PLoS Computational Biology·Daniel J LaydonBecca Asquith
Dec 11, 2014·Annual Review of Immunology·Jamie RossjohnJames McCluskey
Jan 27, 2015·Cellular & Molecular Immunology·Meriem AttafAndrew K Sewell
Apr 2, 2015·Proceedings of the National Academy of Sciences of the United States of America·Diego ChowellKaren S Anderson
Apr 29, 2015·Proceedings of the National Academy of Sciences of the United States of America·Andreas MayerAleksandra M Walczak
Apr 30, 2015·Nature Methods·Dmitriy A BolotinDmitriy M Chudakov
Aug 21, 2015·Science Translational Medicine·Bryan HowieHarlan S Robins
Oct 29, 2015·Trends in Immunology·Victor GreiffSai T Reddy
Nov 26, 2015·PLoS Computational Biology·Mikhail ShugayDmitriy M Chudakov
Feb 11, 2016·Immunology and Cell Biology·Auda A EltahlaFabio Luciani
Apr 6, 2016·Frontiers in Immunology·Nicolas DegauqueJean-Paul Soulillou
May 18, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Olga V BritanovaDmitriy M Chudakov
May 21, 2016·Science·Erlend StrønenTon N Schumacher
Jun 15, 2016·BMC Genomics·Dmitriy V BagaevMikhail Shugay
Jul 5, 2016·Nature Reviews. Genetics·Hubert HacklZlatko Trajanoski
May 10, 2017·Molecular Therapy. Methods & Clinical Development·Hema DavePatrick J Hanley
Jun 22, 2017·Nature·Jacob GlanvilleMark M Davis
Jul 7, 2017·PLoS Computational Biology·Mikhail V PogorelyyAleksandra M Walczak
Oct 5, 2017·Nucleic Acids Research·Mikhail ShugayDmitriy M Chudakov
Feb 10, 2018·Nature Communications·Quentin MarcouAleksandra M Walczak
Mar 14, 2018·ELife·Mikhail V PogorelyyAleksandra M Walczak

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Citations

Sep 6, 2019·ELife·Kristian DavidsenFrederick A Matsen
Sep 29, 2020·Frontiers in Immunology·Ido SpringerYoram Louzoun
May 7, 2019·Frontiers in Immunology·Masato Ogishi, Hiroshi Yotsuyanagi
May 15, 2020·F1000Research·Chloe H Lee, Hashem Koohy
Oct 17, 2019·Frontiers in Immunology·Mikhail V Pogorelyy, Mikhail Shugay
Jan 20, 2021·Advanced Drug Delivery Reviews·Muhammad Saqib SohailMatthew R McKay
Nov 17, 2020·Frontiers in Immunology·Chloe H LeeHashem Koohy
Jul 27, 2021·PLoS Computational Biology·Shirit DvorkinYoram Louzoun

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Methods Mentioned

BETA
RepSeq
flow cytometry
single-cell sequencing

Software Mentioned

MiXCR
VDJtools
R
VDJtools PoolSamples
Kidera
RepSeq
VDJtools FilterNonFunctional
MiXCR Align

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