Antihomotypic affinity maturation improves human B cell responses against a repetitive epitope

被引：78

作者：

Imkeller, Katharina ^{[1
,2
]}

Scally, Stephen W. ^{[3
]}

Bosch, Alexandre ^{[3
]}

Marti, Gemma Pidelaserra ^{[1
,2
]}

Costa, Giulia ^{[4
]}

Triller, Gianna ^{[1
]}

Murugan, Rajagopal ^{[1
]}

Renna, Valerio ^{[5
]}

Jumaa, Hassan ^{[5
]}

Kremsner, Peter G. ^{[6
,7
]}

Sim, B. Kim Lee ^{[8
]}

Hoffman, Stephen L. ^{[8
]}

Mordmueller, Benjamin ^{[6
,7
]}

Levashina, Elena A. ^{[4
]}

Julien, Jean-Philippe ^{[3
,9
,10
]}

Wardemann, Hedda ^{[1
]}

机构：

[1] German Canc Res Inst, Cell Immunol B, Heidelberg, Germany

[2] Heidelberg Univ, Fac Biosci, Heidelberg, Germany

[3] Hosp Sick Children, Res Inst, Program Mol Med, Toronto, ON, Canada

[4] Max Planck Inst Infect Biol, Vector Biol Unit, Berlin, Germany

[5] Univ Med Ctr Ulm, Inst Immunol, Ulm, Germany

[6] Univ Tubingen, Inst Trop Med, Partner Site, Tubingen, Germany

[7] Univ Tubingen, German Ctr Infect Res, Partner Site, Tubingen, Germany

[8] Sanaria, Rockville, MD USA

[9] Univ Toronto, Dept Biochem, Toronto, ON, Canada

[10] Univ Toronto, Dept Immunol, Toronto, ON, Canada

来源：

SCIENCE | 2018年 / 360卷 / 6395期

基金：

比尔及梅琳达.盖茨基金会; 加拿大健康研究院; 加拿大自然科学与工程研究理事会; 加拿大创新基金会;

关键词：

PLASMODIUM-FALCIPARUM; MALARIA PARASITE; CIRCUMSPOROZOITE PROTEIN; MONOCLONAL-ANTIBODIES; SURFACE-ANTIGEN; INFECTION; SPOROZOITE; VACCINE; REPERTOIRE; SEQUENCE;

D O I：

10.1126/science.aar5304

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Affinity maturation selects B cells expressing somatically mutated antibody variants with improved antigen-binding properties to protect from invading pathogens. We determined the molecular mechanism underlying the clonal selection and affinity maturation of human B cells expressing protective antibodies against the circumsporozoite protein of the malaria parasite Plasmodium falciparum (PfCSP). We show in molecular detail that the repetitive nature of PfCSP facilitates direct homotypic interactions between two PfCSP repeat-bound monoclonal antibodies, thereby improving antigen affinity and B cell activation. These data provide a mechanistic explanation for the strong selection of somatic mutations that mediate homotypic antibody interactions after repeated parasite exposure in humans. Our findings demonstrate a different mode of antigen-mediated affinity maturation to improve antibody responses to PfCSP and presumably other repetitive antigens.

引用

页码：1358 / 1362

页数：5

共 21 条

[1] STRUCTURE OF THE GENE ENCODING THE IMMUNODOMINANT SURFACE-ANTIGEN ON THE SPOROZOITE OF THE HUMAN MALARIA PARASITE PLASMODIUM-FALCIPARUM [J].

DAME, JB ;

WILLIAMS, JL ;

MCCUTCHAN, TF ;

WEBER, JL ;

WIRTZ, RA ;

HOCKMEYER, WT ;

MALOY, WL ;

HAYNES, JD ;

SCHNEIDER, I ;

ROBERTS, D ;

SANDERS, GS ;

REDDY, EP ;

DIGGS, CL ;

MILLER, LH .

SCIENCE, 1984, 225 (4662) :593-599

[2] Repetitive sequences in malaria parasite proteins [J].

Davies, Heledd M. ;

Nofal, Stephanie D. ;

McLaughlin, Emilia J. ;

Osborne, Andrew R. .

FEMS MICROBIOLOGY REVIEWS, 2017, 41 (06) :923-940

[3] In-depth determination and analysis of the human paired heavy- and light-chain antibody repertoire [J].

DeKosky, Brandon J. ;

Kojima, Takaaki ;

Rodin, Alexa ;

Charab, Wissam ;

Ippolito, Gregory C. ;

Ellington, Andrew D. ;

Georgiou, George .

NATURE MEDICINE, 2015, 21 (01) :86-91

[4] DNA CLONING OF PLASMODIUM-FALCIPARUM CIRCUMSPOROZOITE GENE - AMINO-ACID-SEQUENCE OF REPETITIVE EPITOPE [J].

ENEA, V ;

ELLIS, J ;

ZAVALA, F ;

ARNOT, DE ;

ASAVANICH, A ;

MASUDA, A ;

QUAKYI, I ;

NUSSENZWEIG, RS .

SCIENCE, 1984, 225 (4662) :628-630

[5] T-dependent B cell responses to Plasmodium induce antibodies that form a high-avidity multivalent complex with the circumsporozoite protein [J].

Fisher, Camilla R. ;

Sutton, Henry J. ;

Kaczmarski, Joe A. ;

McNamara, Hayley A. ;

Clifton, Ben ;

Mitchell, Joshua ;

Cai, Yeping ;

Dups, Johanna N. ;

D'Arcy, Nicholas J. ;

Singh, Mandeep ;

Chuah, Aaron ;

Peat, Thomas S. ;

Jackson, Colin J. ;

Cockburn, Ian A. .

PLOS PATHOGENS, 2017, 13 (07)

[6] Vaccine-induced monoclonal antibodies targeting circumsporozoite protein prevent Plasmodium falciparum infection [J].

Foquet, Lander ;

Hermsen, Cornelus C. ;

van Gemert, Geert-Jan ;

Van Braeckel, Eva ;

Weening, Karin E. ;

Sauerwein, Robert ;

Meuleman, Philip ;

Leroux-Roels, Geert .

JOURNAL OF CLINICAL INVESTIGATION, 2014, 124 (01) :140-144

[7]

Ghasparian A, 2006, CHEM COMMUN, V14, P174, DOI [10.1039/B510812H, DOI 10.1039/B510812H]

[8] Change-O: a toolkit for analyzing large-scale B cell immunoglobulin repertoire sequencing data [J].

Gupta, Namita T. ;

Vander Heiden, Jason A. ;

Uduman, Mohamed ;

Gadala-Maria, Daniel ;

Yaari, Gur ;

Kleinstein, Steven H. .

BIOINFORMATICS, 2015, 31 (20) :3356-3358

[9] Antigen clasping by two antigen-binding sites of an exceptionally specific antibody for histone methylation [J].

Hattori, Takamitsu ;

Lai, Darson ;

Dementieva, Irina S. ;

Montano, Sherwin P. ;

Kurosawa, Kohei ;

Zheng, Yupeng ;

Akin, Louesa R. ;

Swist-Rosowska, Kalina M. ;

Grzybowski, Adrian T. ;

Koide, Akiko ;

Krajewski, Krzysztof ;

Strahl, Brian D. ;

Kelleher, Neil L. ;

Ruthenburg, Alexander J. ;

Koide, Shohei .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2016, 113 (08) :2092-2097

[10] A human monoclonal antibody prevents malaria infection by targeting a new site of vulnerability on the parasite [J].

Kisalu, Neville K. ;

Idris, Azza H. ;

Weidle, Connor ;

Flores-Garcia, Yevel ;

Flynn, Barbara J. ;

Sack, Brandon K. ;

Murphy, Sean ;

Schoen, Arne ;

Freire, Ernesto ;

Francica, Joseph R. ;

Miller, Alex B. ;

Gregory, Jason ;

March, Sandra ;

Liao, Hua-Xin ;

Haynes, Barton F. ;

Wiehe, Kevin ;

Trama, Ashley M. ;

Saunders, Kevin O. ;

Gladden, Morgan A. ;

Monroe, Anthony ;

Bonsignori, Mattia ;

Kanekiyo, Masaru ;

Wheatley, Adam K. ;

McDermott, Adrian B. ;

Farney, S. Katie ;

Chuang, Gwo-Yu ;

Zhang, Baoshan ;

Kc, Natasha ;

Chakravarty, Sumana ;

Kwong, Peter D. ;

Sinnis, Photini ;

Bhatia, Sangeeta N. ;

Kappe, Stefan H. I. ;

Sim, B. Kim Lee ;

Hoffman, Stephen L. ;

Zavala, Fidel ;

Pancera, Marie ;

Seder, Robert A. .

NATURE MEDICINE, 2018, 24 (04) :408-+

← 1 2 3 →