Entropic analysis of antigen-specific CDR3 domains identifies essential binding motifs shared by CDR3s with different antigen specificities.

Receptors, Antigen, T-Cell, alpha-beta / genetics Entropy Amino Acid Sequence Receptors, Antigen, T-Cell Antigens
CDR3 domains SARS-COV-2 T cell receptors T cells antigens

Journal

Cell systems
ISSN: 2405-4720
Titre abrégé: Cell Syst
Pays: United States
ID NLM: 101656080

Informations de publication

Date de publication:
19 04 2023
Historique:
received: 15 11 2021
revised: 01 09 2022
accepted: 01 03 2023
medline: 24 4 2023
pubmed: 1 4 2023
entrez: 31 3 2023
Statut: ppublish

Résumé

Antigen-specific T cell receptor (TCR) sequences can have prognostic, predictive, and therapeutic value, but decoding the specificity of TCR recognition remains challenging. Unlike DNA strands that base pair, TCRs bind to their targets with different orientations and different lengths, which complicates comparisons. We present scanning parametrized by normalized TCR length (SPAN-TCR) to analyze antigen-specific TCR CDR3 sequences and identify patterns driving TCR-pMHC specificity. Using entropic analysis, SPAN-TCR identifies 2-mer motifs that decrease the diversity (entropy) of CDR3s. These motifs are the most common patterns that can predict CDR3 composition, and we identify "essential" motifs that decrease entropy in the same CDR3 α or β chain containing the 2-mer, and "super-essential" motifs that decrease entropy in both chains. Molecular dynamics analysis further suggests that these motifs may play important roles in binding. We then employ SPAN-TCR to resolve similarities in TCR repertoires against different antigens using public databases of TCR sequences.

Identifiants

DOI: 10.1016/j.cels.2023.03.001 PMID: 37001518 PMC: PMC10355346
pubmed: 37001518
pii: S2405-4712(23)00057-1
doi: 10.1016/j.cels.2023.03.001
pmc: PMC10355346
mid: NIHMS1887346
pii:
doi:

Substances chimiques

Receptors, Antigen, T-Cell, alpha-beta 0
Receptors, Antigen, T-Cell 0
Antigens 0

Types de publication

Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

273-284.e5

Subventions

Organisme : NCI NIH HHS
ID : R01 CA264090
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA015704
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA097186
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI153559
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001881
Pays : United States

Informations de copyright

Copyright © 2023 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests J.R.H. is a founder and board member of Isoplexis and PACT Pharma. M.M.D. is a member of the Scientific Advisory Board of PACT Pharma.

Références

Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10915-9
pubmed: 1438297
Nature. 1988 Aug 4;334(6181):395-402
pubmed: 3043226
Front Immunol. 2017 Nov 15;8:1500
pubmed: 29187849
Nucleic Acids Res. 2020 Jan 8;48(D1):D1057-D1062
pubmed: 31588507
Nature. 2021 Aug;596(7873):583-589
pubmed: 34265844
Proc Natl Acad Sci U S A. 2016 Mar 1;113(9):E1276-85
pubmed: 26884163
Nucleic Acids Res. 2018 Jul 2;46(W1):W396-W401
pubmed: 29790966
Immunity. 2011 Nov 23;35(5):681-93
pubmed: 22101157
J Immunol. 1994 May 15;152(10):5109-19
pubmed: 8176227
Front Immunol. 2019 Jul 31;10:1516
pubmed: 31417541
Annu Rev Immunol. 2019 Apr 26;37:547-570
pubmed: 30699000
BMC Biotechnol. 2017 Jul 10;17(1):61
pubmed: 28693542
Nat Commun. 2022 Mar 10;13(1):1265
pubmed: 35273146
Trends Biotechnol. 2017 Mar;35(3):203-214
pubmed: 28341036
Sci Adv. 2021 May 14;7(20):
pubmed: 33990328
Nat Commun. 2015 Sep 01;6:8081
pubmed: 26324409
PLoS Biol. 2019 Jun 13;17(6):e3000314
pubmed: 31194732
Ecology. 2012 Mar;93(3):477-89
pubmed: 22624203
Nucleic Acids Res. 2018 Jan 4;46(D1):D406-D412
pubmed: 29087479
Bioinformatics. 2020 Feb 1;36(3):897-903
pubmed: 31373607
Philos Trans R Soc Lond B Biol Sci. 2015 Aug 19;370(1675):
pubmed: 26150657
Nat Struct Mol Biol. 2017 Apr;24(4):395-406
pubmed: 28250417
Cell. 2020 Oct 29;183(3):818-834.e13
pubmed: 33038342
Nature. 2017 Jul 6;547(7661):94-98
pubmed: 28636589
Cell Physiol Biochem. 2016;39(2):651-67
pubmed: 27442436
Nat Mach Intell. 2021 Oct;3(10):864-875
pubmed: 36003885
Genome Med. 2018 Aug 25;10(1):68
pubmed: 30144804
J Immunol. 2017 Oct 1;199(7):2203-2213
pubmed: 28923982
Cell. 2005 Aug 12;122(3):333-6
pubmed: 16096054
PLoS Comput Biol. 2019 Sep 9;15(9):e1007338
pubmed: 31498801
Nat Methods. 2015 May;12(5):380-1
pubmed: 25924071
Nucleic Acids Res. 2018 Jan 4;46(D1):D419-D427
pubmed: 28977646
Nat Biotechnol. 2020 Oct;38(10):1194-1202
pubmed: 32341563
Trends Immunol. 2014 Oct 8;35(12):581-590
pubmed: 25306219
PLoS One. 2016 Nov 11;11(11):e0166126
pubmed: 27835690
J Biol Chem. 2009 Oct 2;284(40):27281-9
pubmed: 19605354
Sci Rep. 2021 Jul 12;11(1):14275
pubmed: 34253751
Lab Chip. 2019 Sep 10;19(18):3011-3021
pubmed: 31502632
Nucleic Acids Res. 2015 Jan;43(Database issue):D405-12
pubmed: 25300482
Nat Immunol. 2005 Feb;6(2):171-80
pubmed: 15640805
Biotechniques. 2017 Mar 1;62(3):123-130
pubmed: 28298179
Front Physiol. 2021 Sep 08;12:730908
pubmed: 34566692
Proc Natl Acad Sci U S A. 2020 Jun 16;117(24):13659-13669
pubmed: 32482872
Haematologica. 2019 Dec;104(12):e577-e580
pubmed: 31018979
Brief Bioinform. 2021 Jul 20;22(4):
pubmed: 33346826
Annu Rev Biophys Biomol Struct. 2002;31:121-49
pubmed: 11988465
Mol Syst Biol. 2020 Aug;16(8):e9416
pubmed: 32779888
Elife. 2021 Jan 05;10:
pubmed: 33399535
Bioinformatics. 2017 Sep 15;33(18):2924-2929
pubmed: 28481982
Science. 2015 Apr 3;348(6230):69-74
pubmed: 25838375
Proc Natl Acad Sci U S A. 2012 Nov 6;109(45):18517-22
pubmed: 23091041
Sci Rep. 2017 Jun 16;7(1):3663
pubmed: 28623251
Nature. 2017 Jul 6;547(7661):89-93
pubmed: 28636592
Immunity. 2016 Oct 18;45(4):749-760
pubmed: 27717799
Sci Transl Med. 2015 Aug 19;7(301):301ra131
pubmed: 26290413
Front Immunol. 2019 Aug 28;10:2080
pubmed: 31555288
Proc Natl Acad Sci U S A. 2015 Apr 7;112(14):E1754-62
pubmed: 25831525
Front Immunol. 2021 Mar 11;12:640725
pubmed: 33777034
BMC Bioinformatics. 2009 Nov 30;10:394
pubmed: 19948066
Nat Biotechnol. 2016 Oct;34(10):1037-1045
pubmed: 27571370
Annu Rev Immunol. 2006;24:419-66
pubmed: 16551255
PLoS Comput Biol. 2013 Oct;9(10):e1003266
pubmed: 24204222
Cell Rep. 2017 Apr 18;19(3):569-583
pubmed: 28423320
Nucleic Acids Res. 2017 Dec 1;45(21):12565-12576
pubmed: 29040720
J Mol Biol. 1990 Oct 5;215(3):403-10
pubmed: 2231712
Cell Rep Med. 2021 Feb 16;2(2):100192
pubmed: 33495756
Bioinformatics. 2021 Jul 12;37(Suppl_1):i237-i244
pubmed: 34252922
Front Immunol. 2018 Feb 21;9:224
pubmed: 29515569

Auteurs

Alexander M Xu (AM)

Institute for Systems Biology, Seattle, WA 98109, USA; Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. Electronic address: alexander.xu@cshs.org.

William Chour (W)

Institute for Systems Biology, Seattle, WA 98109, USA; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA; Keck School of Medicine, University of Southern California, Los Angeles, CA 91125, USA.

Diana C DeLucia (DC)

Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.

Yapeng Su (Y)

Institute for Systems Biology, Seattle, WA 98109, USA; Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.

Ana Jimena Pavlovitch-Bedzyk (AJ)

Computational and Systems Immunology Program, Stanford University School of Medicine, Stanford, CA 94305, USA.

Rachel Ng (R)

Institute for Systems Biology, Seattle, WA 98109, USA.

Yusuf Rasheed (Y)

Institute for Systems Biology, Seattle, WA 98109, USA.

Mark M Davis (MM)

Computational and Systems Immunology Program, Stanford University School of Medicine, Stanford, CA 94305, USA; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.

John K Lee (JK)

Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA 98195, USA.

James R Heath (JR)

Institute for Systems Biology, Seattle, WA 98109, USA. Electronic address: jim.heath@isbscience.org.

Articles similaires

Decoding the genomic terrain: functional insights into 14 chemosensory proteins in whitefly Bemisia tabaci Asia II-1.

M N Rudra Gouda, Sabtharishi Subramanian
1.00
Animals Hemiptera Insect Proteins Phylogeny Insecticides

More T cell receptors to the RAScue in cancer?

Eric Tran
1.00
Humans Receptors, Antigen, T-Cell Proto-Oncogene Proteins p21(ras) Pancreatic Neoplasms T-Lymphocytes

A head-to-head comparison of MM/PBSA and MM/GBSA in predicting binding affinities for the CB

Mei Qian Yau, Clarence W Y Liew, Jing Hen Toh et al.
1.00
Receptor, Cannabinoid, CB1 Ligands Molecular Dynamics Simulation Protein Binding Thermodynamics

Motif mapping during chickpea germination reveals a complex sequential activation of different proteolytic activities.

Indrani Bera, Michael O'Sullivan, Caitriona Scaife et al.
1.00
Cicer Germination Proteolysis Seeds Plant Proteins

Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs immunologiques › Récepteurs aux antigènes › Récepteurs aux antigènes des cellules T › Récepteur lymphocytaire T antigène, alpha-bêta › Entropic analysis of antigen-specific CDR3...
questionsmedicales.fr › Phénomènes physiques › Thermodynamique › Entropie › Entropic analysis of antigen-specific CDR3...
questionsmedicales.fr › Sciences de l'information › Sources d'information › Services d'information › Documentation › Données de séquences moléculaires › Séquence d'acides aminés › Entropic analysis of antigen-specific CDR3...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs immunologiques › Récepteurs aux antigènes › Récepteurs aux antigènes des cellules T › Entropic analysis of antigen-specific CDR3...
questionsmedicales.fr › Facteurs biologiques › Antigènes › Entropic analysis of antigen-specific CDR3...