Gunilla Karlsson Hedestam Group
We are interested in understanding how early interactions between foreign antigens and immune cells influence the development of specific B cell responses and how such responses evolve over time. In several projects, we study properties of vaccine-induced B cell responses at the clonal level by single-cell sorting B cells for sequence analysis of antibody V(D)J transcripts and for isolation of antigen-specific monoclonal antibodies. We also apply next generation sequencing to analyze antibody repertoires and to trace specific antibody lineages in specific immune compartments. Because gene assignment is a critical first step of lineage tracing, and there is considerable genetic variation in germline V genes/alleles between subjects, we recently developed a computational tool that allows the generation of individualized germline V gene databases, IgDiscover. This is a major technical advance that will enable the use of individualized germline databases to become a standard element of high quality immunological studies in both humans and experimental animals. By applying these methods we can obtain new and highly detailed information about the establishment of long-lived immunity in response to immunization. We also study mice with specific mutations in pathways affecting B cell development or activation, allowing us to investigate processes regulating B cell selection and differentiation.
Affiliated project leaders
NF-κB signaling in B-1 cell development.
Ann. N. Y. Acad. Sci. 2015 Dec;1362():39-47
Real-time resolution of point mutations that cause phenovariance in mice.
Proc. Natl. Acad. Sci. U.S.A. 2015 Feb;112(5):E440-9
Diverse antibody genetic and recognition properties revealed following HIV-1 envelope glycoprotein immunization.
J. Immunol. 2015 Jun;194(12):5903-14
Slc15a4 function is required for intact class switch recombination to IgG2c in response to TLR9 stimulation.
Immunol. Cell Biol. 2015 Feb;93(2):136-46
MAVS, cGAS, and endogenous retroviruses in T-independent B cell responses.
Science 2014 Dec;346(6216):1486-92
B-1a transitional cells are phenotypically distinct and are lacking in mice deficient in IκBNS.
Proc. Natl. Acad. Sci. U.S.A. 2014 Sep;111(39):E4119-26
Enhanced HIV-1 immunotherapy by commonly arising antibodies that target virus escape variants.
J. Exp. Med. 2014 Nov;211(12):2361-72
HIV-1 receptor binding site-directed antibodies using a VH1-2 gene segment orthologue are activated by Env trimer immunization.
PLoS Pathog. 2014 Aug;10(8):e1004337
Single-cell and deep sequencing of IgG-switched macaque B cells reveal a diverse Ig repertoire following immunization.
J. Immunol. 2014 Apr;192(8):3637-44
Vaccine-elicited primate antibodies use a distinct approach to the HIV-1 primary receptor binding site informing vaccine redesign.
Proc. Natl. Acad. Sci. U.S.A. 2014 Feb;111(7):E738-47
A forward genetic screen reveals roles for Nfkbid, Zeb1, and Ruvbl2 in humoral immunity.
Proc. Natl. Acad. Sci. U.S.A. 2012 Jul;109(31):12286-93
High-resolution definition of vaccine-elicited B cell responses against the HIV primary receptor binding site.
Sci Transl Med 2012 Jul;4(142):142ra96
BLyS-mediated modulation of naive B cell subsets impacts HIV Env-induced antibody responses.
J. Immunol. 2012 Jun;188(12):6018-26
Soluble HIV-1 Env trimers in adjuvant elicit potent and diverse functional B cell responses in primates.
J. Exp. Med. 2010 Aug;207(9):2003-17
A mutation of Ikbkg causes immune deficiency without impairing degradation of IkappaB alpha.
Proc. Natl. Acad. Sci. U.S.A. 2010 Feb;107(7):3046-51
The challenges of eliciting neutralizing antibodies to HIV-1 and to influenza virus.
Nat. Rev. Microbiol. 2008 Feb;6(2):143-55
Jonathan Coquet Project:
PhD students (name and year of graduation)
Åsa defended her PhD in 2007 after which she received the Jonas Söderqvist’s Prize for basic research in virology and immunology. Åsa moved on to a post-doctoral position at the University of Heidelberg in Germany, where she is now active as a senior research scientist in the field of immunology and diabetes.
Mattias defended his PhD in 2008. Part of his doctoral research was carried out at the National Institutes of Health in Washington. After this, he received an Early career investigator AMFAR award for post-doctoral work, which was carried out at Karolinska Institutet. He recently obtained a position as Assistant Professor at Umeå University where he now leads his own research group.
Pia defended her PhD in 2012 after which she obtained 3 years of funding from the Swedish Research Council to pursue a post-doc at the Rockefeller University in New York. Pia is currently active in several research consortia including CHAVI-ID, as a member of the Nussenzweig laboratory.
Christopher defended his PhD in 2012 and in the last year of his studies he was awarded the Dimitris N. Chorafas Foundation Prize. He subsequently also received the Jonas Söderqvist’s Prize for basic research in virology and immunology and Sven Gard’s prize for best thesis in virology. He is currently pursuing a post-doc in the Brink laboratory at the Garvan Institute in Sydney, funded by the Swedish Research Council.
Cornelia Gujer, 2011
Kai Eng, 2012
Lina Josefsson, 2013
Lotta Pramanik Sollerkvist, 2014
MSc students (name and year of graduation)
Christopher Sundling, 2007
Martina Soldemo, 2009
Nick Huynh, 2011
Max Reiss, 2011
Flavio Lombardo, 2013
Néstor Vázquez Bernat, 2014
Sharesta Khoenkhoen, 2014
John Mascola, Vaccine Research Center, NIH
Richard Wyatt, The Scripps Research Center
Larry Shapiro, Columbia University
Michael Cancro, University of Pennsylvania
Lynn Morris, Johannesburg
Bruce Beutler, UT Southwestern
Roberto Cattaneo, Mayo Clinic
Michel Nussenzweig, Rockefeller University
Joe Sodroski/Navid Madani, Harvard Medical School
Joan Yuan, Lund University
Robin Löving/Henrik Garoff, Dept. of Biosciences and Nutrition, KI
Karin Loré, CIM, KI
Mikael Karlsson, MTC, KI
Stephen Malin, Dept. of Medicine, KI
Mats Persson, Department of Clinical Neuroscience, KI
We gratefully receive financial support for our research from several organizations, currently from:
Swedish Research Council (Vetenskapsrådet, VR)
International AIDS Vaccine Initiative (IAVI)
Karolinska Institutet (KID medel)
National Institutes of Health (NIH)
KI-Mayo Clinic Collaborative Grants
David och Astrid Hageléns stiftelse
European Union, H2020
Department of Microbiology, Tumor and Cell Biology Karolinska Institutet P.O. Box 280 Nobels väg 16 SE-171 77 Stockholm, Sweden