Conformational diversity facilitates antibody mutation trajectories and discrimination between foreign and self-antigens.

Szczegóły
Abstrakt

Tytuł:: Conformational diversity facilitates antibody mutation trajectories and discrimination between foreign and self-antigens.
Autorzy:: Burnett DL; Garvan Institute of Medical Research, University of New South Wales (UNSW) Sydney, Darlinghurst, NSW 2010, Australia.; St Vincent's Clinical School, Department of Medicine, UNSW Sydney, NSW 2052, Australia.
Schofield P; Garvan Institute of Medical Research, University of New South Wales (UNSW) Sydney, Darlinghurst, NSW 2010, Australia.; St Vincent's Clinical School, Department of Medicine, UNSW Sydney, NSW 2052, Australia.
Langley DB; Garvan Institute of Medical Research, University of New South Wales (UNSW) Sydney, Darlinghurst, NSW 2010, Australia.
Jackson J; Garvan Institute of Medical Research, University of New South Wales (UNSW) Sydney, Darlinghurst, NSW 2010, Australia.
Bourne K; Garvan Institute of Medical Research, University of New South Wales (UNSW) Sydney, Darlinghurst, NSW 2010, Australia.
Wilson E; Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3168, Australia.
Porebski BT; Medical Research Council Laboratory of Molecular Biology, CB2 OQH Cambridge, United Kingdom.
Buckle AM; Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3168, Australia.
Brink R; Garvan Institute of Medical Research, University of New South Wales (UNSW) Sydney, Darlinghurst, NSW 2010, Australia.; St Vincent's Clinical School, Department of Medicine, UNSW Sydney, NSW 2052, Australia.
Goodnow CC; Garvan Institute of Medical Research, University of New South Wales (UNSW) Sydney, Darlinghurst, NSW 2010, Australia; .; St Vincent's Clinical School, Department of Medicine, UNSW Sydney, NSW 2052, Australia.; UNSW Cellular Genomics Futures Institute, UNSW Sydney, NSW 2052, Australia.
Christ D; Garvan Institute of Medical Research, University of New South Wales (UNSW) Sydney, Darlinghurst, NSW 2010, Australia; .; St Vincent's Clinical School, Department of Medicine, UNSW Sydney, NSW 2052, Australia.
Źródło:: Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2020 Sep 08; Vol. 117 (36), pp. 22341-22350. Date of Electronic Publication: 2020 Aug 27.
Typ publikacji:: Journal Article; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Original Publication: Washington, DC : National Academy of Sciences
MeSH Terms:: Antibodies*/chemistry
Antibodies*/genetics
Antibodies*/metabolism
Autoantigens*/chemistry
Autoantigens*/metabolism
Antibody Diversity/*genetics
Gene Rearrangement, B-Lymphocyte/*genetics
Mutation/*genetics
Animals ; Antibody Affinity/genetics ; Autoantibodies/chemistry ; Autoantibodies/genetics ; Autoantibodies/metabolism ; Complementarity Determining Regions/genetics ; Immunity, Humoral/genetics ; Mice ; Models, Molecular ; Protein Conformation ; Somatic Hypermutation, Immunoglobulin/genetics
References:: J Exp Med. 2006 Oct 30;203(11):2419-24. (PMID: 17030950)
Structure. 1999 Feb 15;7(2):131-42. (PMID: 10368281)
Structure. 2016 Jan 5;24(1):148-157. (PMID: 26712277)
J Exp Med. 2006 Apr 17;203(4):1081-91. (PMID: 16606676)
Proc Natl Acad Sci U S A. 2010 Oct 19;107(42):17880-7. (PMID: 20876137)
J Mol Biol. 2008 Apr 11;377(5):1518-28. (PMID: 18336836)
BMC Struct Biol. 2018 Aug 22;18(1):10. (PMID: 30134879)
Biochemistry. 2002 Feb 19;41(7):2130-9. (PMID: 11841203)
FEBS Lett. 1996 Apr 1;383(3):251-4. (PMID: 8925907)
Acta Crystallogr D Biol Crystallogr. 2013 Jul;69(Pt 7):1204-14. (PMID: 23793146)
J Mol Graph Model. 2001;19(1):26-59. (PMID: 11381529)
Acta Crystallogr D Biol Crystallogr. 2011 Apr;67(Pt 4):235-42. (PMID: 21460441)
Immunity. 2012 Nov 16;37(5):893-904. (PMID: 23142780)
J Clin Invest. 2014 Jan;124(1):140-4. (PMID: 24292709)
Annu Rev Microbiol. 1987;41:181-208. (PMID: 3318667)
Acta Crystallogr D Biol Crystallogr. 2011 Apr;67(Pt 4):355-67. (PMID: 21460454)
Acta Crystallogr D Biol Crystallogr. 2011 Apr;67(Pt 4):282-92. (PMID: 21460446)
Science. 2005 Jun 24;308(5730):1906-8. (PMID: 15860590)
J Mol Biol. 2000 Feb 4;295(5):1275-88. (PMID: 10653703)
Infect Immun. 2012 Dec;80(12):4177-85. (PMID: 22966050)
Science. 1997 Jun 13;276(5319):1665-9. (PMID: 9180069)
Nat Rev Mol Cell Biol. 2005 Mar;6(3):197-208. (PMID: 15738986)
Semin Immunol. 1989 Nov;1(2):125-35. (PMID: 15630814)
Retrovirology. 2018 Jul 28;15(1):53. (PMID: 30055635)
Science. 2003 Feb 28;299(5611):1362-7. (PMID: 12610298)
Nature. 2002 Dec 12;420(6916):678-82. (PMID: 12478295)
PLoS Pathog. 2019 Dec 16;15(12):e1008165. (PMID: 31841553)
J Mol Biol. 2003 Jul 18;330(4):651-6. (PMID: 12850137)
Cell. 2013 Mar 28;153(1):126-38. (PMID: 23540694)
Nat Protoc. 2018 Jan;13(1):99-117. (PMID: 29240734)
Adv Immunol. 1995;59:279-368. (PMID: 7484462)
Parasite Immunol. 1986 Nov;8(6):529-39. (PMID: 3543808)
Science. 2018 Apr 13;360(6385):223-226. (PMID: 29650674)
J Biol Chem. 2003 Feb 14;278(7):5410-8. (PMID: 12444085)
J Biol Chem. 2005 Apr 8;280(14):14114-21. (PMID: 15659390)
Proc Natl Acad Sci U S A. 1990 Nov;87(21):8403-7. (PMID: 2236048)
Biochemistry. 1990 Aug 28;29(34):7828-37. (PMID: 2261440)
Science. 2003 Sep 5;301(5638):1374-7. (PMID: 12920303)
Acta Crystallogr D Biol Crystallogr. 1998 Sep 1;54(Pt 5):767-80. (PMID: 9757091)
Science. 2014 May 9;344(6184):588-9. (PMID: 24812389)
Nat Protoc. 2012 Feb 02;7(2):364-73. (PMID: 22301775)
Cell. 1992 Mar 6;68(5):869-77. (PMID: 1547488)
Lancet Infect Dis. 2011 Feb;11(2):102-9. (PMID: 21237715)
Nature. 1984 Sep 13-19;311(5982):123-6. (PMID: 6206398)
Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):486-501. (PMID: 20383002)
Acta Crystallogr D Struct Biol. 2017 Nov 1;73(Pt 11):910-920. (PMID: 29095163)
J Biol Chem. 1996 Jan 19;271(3):1379-84. (PMID: 8576127)
Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10370-4. (PMID: 7937957)
Biochemistry. 2004 Jun 1;43(21):6663-9. (PMID: 15157100)
Biochemistry. 2009 Feb 17;48(6):1390-8. (PMID: 19166328)
Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):6803-7. (PMID: 1495968)
Trends Biochem Sci. 1993 May;18(5):181-6. (PMID: 8328018)
Acta Crystallogr D Biol Crystallogr. 2011 Apr;67(Pt 4):271-81. (PMID: 21460445)
Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):125-32. (PMID: 20124692)
Immunity. 2018 Jan 16;48(1):133-146.e6. (PMID: 29287996)
J Autoimmun. 2007 Dec;29(4):219-28. (PMID: 17888628)
J Exp Med. 2003 Apr 7;197(7):845-60. (PMID: 12668643)
Elife. 2018 Feb 14;7:. (PMID: 29442996)
Nat Struct Biol. 1999 Feb;6(2):141-5. (PMID: 10048925)
Cell Rep. 2018 May 29;23(9):2568-2581. (PMID: 29847789)
Immunol Cell Biol. 2017 Oct;95(9):775-788. (PMID: 28611475)
Mol Immunol. 2009 Dec;47(2-3):457-64. (PMID: 19781789)
PLoS One. 2015 Mar 05;10(3):e0119899. (PMID: 25742002)
J Virol. 2015 Oct 14;90(1):611-5. (PMID: 26468526)
Nature. 1965 May 22;206(4986):757-61. (PMID: 5891407)
J Appl Crystallogr. 2007 Aug 1;40(Pt 4):658-674. (PMID: 19461840)
Front Immunol. 2019 Jan 07;9:3065. (PMID: 30666252)
Cell. 2014 Feb 13;156(4):633-48. (PMID: 24529371)
J Biol Chem. 2019 Apr 5;294(14):5616-5631. (PMID: 30728245)
Proteins. 2009 Oct;77(1):191-201. (PMID: 19434752)
J Biol Chem. 1991 Jul 5;266(19):12599-603. (PMID: 2061330)
Grant Information:: MC_U105178804 United Kingdom MRC_ Medical Research Council
Contributed Indexing:: Keywords: affinity maturation; autoantibody redemption; clonal selection; humoral immunity; somatic hypermutation
Substance Nomenclature:: 0 (Antibodies)
0 (Autoantibodies)
0 (Autoantigens)
0 (Complementarity Determining Regions)
Entry Date(s):: Date Created: 20200829 Date Completed: 20201030 Latest Revision: 20210310
Update Code:: 20240105
PubMed Central ID:: PMC7486785
DOI:: 10.1073/pnas.2005102117
PMID:: 32855302
: Czasopismo naukowe

Conformational diversity and self-cross-reactivity of antigens have been correlated with evasion from neutralizing antibody responses. We utilized single cell B cell sequencing, biolayer interferometry and X-ray crystallography to trace mutation selection pathways where the antibody response must resolve cross-reactivity between foreign and self-proteins bearing near-identical contact surfaces, but differing in conformational flexibility. Recurring antibody mutation trajectories mediate long-range rearrangements of framework (FW) and complementarity determining regions (CDRs) that increase binding site conformational diversity. These antibody mutations decrease affinity for self-antigen 19-fold and increase foreign affinity 67-fold, to yield a more than 1,250-fold increase in binding discrimination. These results demonstrate how conformational diversity in antigen and antibody does not act as a barrier, as previously suggested, but rather facilitates high affinity and high discrimination between foreign and self.
Competing Interests: The authors declare no competing interest.
(Copyright © 2020 the Author(s). Published by PNAS.)

Informacja