Converging evolution leads to near maximal junction diversity through parallel mechanisms in B and T cell receptors

Physical Biology
Jennifer I C BenichouYoram Louzoun

Abstract

T and B cell receptor (TCR and BCR) complementarity determining region 3 (CDR3) genetic diversity is produced through multiple diversification and selection stages. Potential holes in the CDR3 repertoire were argued to be linked to immunodeficiencies and diseases. In contrast with BCRs, TCRs have practically no Dβ germline genetic diversity, and the question emerges as to whether they can produce a diverse CDR3 repertoire. In order to address the genetic diversity of the adaptive immune system, appropriate quantitative measures for diversity and large-scale sequencing are required. Such a diversity method should incorporate the complex diversification mechanisms of the adaptive immune response and the BCR and TCR loci structure. We combined large-scale sequencing and diversity measures to show that TCRs have a near maximal CDR3 genetic diversity. Specifically, TCR have a larger junctional and V germline diversity, which starts more 5' in Vβ than BCRs. Selection decreases the TCR repertoire diversity, but does not affect BCR repertoire. As a result, TCR is as diverse as BCR repertoire, with a biased CDR3 length toward short TCRs and long BCRs. These differences suggest parallel converging evolutionary tracks to reach the require...Continue Reading

References

Aug 4, 1988·Nature·M M Davis, P J Bjorkman
Jul 1, 1987·Molecular Biology and Evolution·N Saitou, M Nei
Apr 14, 1983·Nature·S Tonegawa
Jan 1, 1995·Annual Review of Immunology·S C JamesonM J Bevan
Mar 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·J K PercusA S Perelson
Jan 1, 1995·Immunogenetics·H G RammenseeS Stevanoviíc
Jan 1, 1994·Annual Review of Immunology·J C CambierM R Clark
Mar 31, 1998·Molecular Immunology·J J StewartS Litwin
Dec 10, 1998·Nucleic Acids Research·M P LefrancD Chaume
Jul 13, 1999·Developmental and Comparative Immunology·H WidholmL Pilström
Nov 5, 1999·Science·T P ArstilaP Kourilsky
Dec 1, 1999·Developmental and Comparative Immunology·M L Lundqvist, L Pilström
Nov 7, 2001·The Journal of Experimental Medicine·J P CabaniolsJ M Kanellopoulos
May 2, 2002·Cell·Craig H BassingFrederick W Alt
Aug 6, 2002·Seminars in Immunology·Yoram LouzounMartin Weigert
Jan 28, 2003·Fish & Shellfish Immunology·Maria Rosaria Coscia, Umberto Oreste
Jun 2, 2005·Molecular Immunology·Yoram LouzounMartin Weigert
Jul 27, 2006·Nature Reviews. Immunology·Valerie H Odegard, David G Schatz
Feb 28, 2008·Nature Reviews. Immunology·Vanessa VenturiMiles P Davenport
May 30, 2009·Bioinformatics·Tal Vider-ShalitYoram Louzoun
Oct 31, 2009·Proceedings of the National Academy of Sciences of the United States of America·Jacob GlanvilleJaume Pons
Nov 13, 2009·Nucleic Acids Research·Paul FlicekStephen M J Searle
Mar 10, 2010·Proceedings of the National Academy of Sciences of the United States of America·Thierry MoraCurtis G Callan
Feb 14, 2012·Marine Genomics·Maria Rosaria CosciaUmberto Oreste
May 4, 2012·Journal of Fish Biology·Ł Głowacki, T Penczak
Sep 19, 2012·Proceedings of the National Academy of Sciences of the United States of America·Anand MuruganCurtis G Callan
Sep 26, 2012·Journal of Mathematical Biology·Grzegorz A Rempala, Michal Seweryn
Feb 23, 2013·Journal of Immunological Methods·Ryan EmersonHarlan Robins
May 1, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jennifer BenichouYoram Louzoun
May 15, 2013·Nucleic Acids Research·Jian YeJames M Ostell
Sep 26, 2013·Frontiers in Immunology·Gilad LibermanYoram Louzoun
Feb 11, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Olga V BritanovaDmitriy M Chudakov
Feb 18, 2014·The Journal of Clinical Investigation·Paolo A MuraroLaurence A Turka
May 27, 2014·Cell·Michael E BirnbaumK Christopher Garcia
Jun 20, 2014·Proceedings of the National Academy of Sciences of the United States of America·Yuval ElhanatiAleksandra M Walczak
Nov 8, 2014·Nucleic Acids Research·Marie-Paule LefrancSofia Kossida

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Citations

Jul 11, 2018·Frontiers in Immunology·Adar ToledanoYoram Louzoun
Jul 27, 2021·PLoS Computational Biology·Shirit DvorkinYoram Louzoun

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