Klas Kärre Group

Project groups within the Klas Kärre Group:

Maria Johansson Project
Sofia Johansson Project
Björn Önfelt Project

Our group has formulated the missing self hypothesis for NK cell recognition, and established a number of experimental models to test and further develop this concept. This original hypothesis states that NK cells can identify abnormal cells by sensing absence or inadequate expression of self MHC class I molecules (see graphics below).

More information on publications and research interests/projects can be found in the respective sections in the left column.

Collaborations

NK, T and Dendritic Cells
Hans-Gustav Ljunggren, Center for Infectious Medicine, CIM Karolinska Institutet, Department of Medicine, Huddinge University Hospital, Stockholm, Sweden.

Tumor Immunology, T-cells and Epitopes
Rolf Kiessling, CCK, Karolinska Unviersity Hospital, Solna, Sweden.

Ly-49 Receptors
Charles Sentman, Immunology, Dartmouth Medical School, Dartmouth College, Hanover, NH, USA.

Protein Expression, Purification and Crystallography
Bob Harris, Neuroimmunology, Center for Molecular Medicine CMM, Karolinska Institutet, Sweden.

NK Cells and Cytomegalovirus
Wayne Yokoyama, Howard Hughes Medical Institute, Rheumatology Division, Department of Medicine, Washington University School of Medicine and Barnes Jewish Hospital, St. Louis, Missouri, USA.

Gerdt Riise, Department of Clinical Virology, Göteborg University, Sahlgrenska Hospital, Göteborg, Sweden.

Annika Linde, SMI/Karolinska Institutet, Stockholm, Sweden.

Cecilia Söderberg-Naucler, Cell and Molecular Immunology, Center for Molecular Medicine CMM, Karolinska Institutet, Sweden.

Eric Vivier, Centre d'Immunologie, INSERM-CNRS de Marseille Luminy, Parc Scientifique de Luminy - Case 906, 13288 Marseille Cedex 9, France.

David Cosman, Molecular Biology, AMGEN Corporation, Seattle, Washington, USA.

Projects

HCMV

Human Cytomegalovirus (HCMV) is a double-stranded DNA-virus, belonging to the herpes viruses. In western countries it infects between 70-80% of the population, usually early in life. Infection under normal circumstances is asymptomatic but the virus establishes life-long latency in the host. Under certain conditions, such as immunosuppression (during cytostatic therapy, transplantation protocols or in AIDS patients), reactivation can occur and give rise to serious or even life-threatening consequences.

However the most fascinating question is how CMV escapes the host immune response for decades and how this fine-tuned equilibrium with the immune system is established. In a permanent co-evolution with the host, CMV evolved a wide array of immunoevasive strategies targeting the immune response on multiple stages. It is estimated that more than 30 viral genes serve the purpose of facilitating immune escape.

CD8+ T cells are known to be crucial for control of the virus, both during primary infection as well as during episodes of reactivation. HCMV has devoted a considerable number of genes ( e.g. US2, US3, US6 and US11, all of which have a different mode of action) to downmodulate MHC class I molecules which, in complex with CMV-derived peptides serve as recognition structures for CD8+ T cells. But the event of MHC class I downmodulation should theoretically render infected cells highly susceptible to NK-cell mediated responses (missing-self recognition, see main page). Yet several groups including our own have reported an even decreased sensitivity to NK cell cytotoxicity after infection of cells with CMV (!) This intriguing finding constitutes the fascinating core question of NK cell - CMV biology (see also cartoon).

To escape NK cells, even in face of markedly reduced MHC class I expression, the virus conceptually has two options:

  1. The delivery of an alternative inhibitory signal to the NK cell (e.g. by virtue of viral class I homologues)
  2. The interference with NK cell activating pathways.

Both alternatives are under investigation in our laboratory.

Publications

         2016

IL-2 in the tumor microenvironment is necessary for Wiskott-Aldrich syndrome protein deficient NK cells to respond to tumors in vivo.
Kritikou J, Dahlberg C, Baptista M, Wagner A, Banerjee P, Gwalani L, et al
Sci Rep 2016 ;6():30636

In vivo engineering of mobilized stem cell grafts with the immunomodulatory drug FTY720 for allogeneic transplantation.
Lakshmikanth T, Heuts F, Muvva S, Wallin R, Persson A, Fauriat C, et al
Eur. J. Immunol. 2016 Jul;46(7):1758-69

Microchip Screening Platform for Single Cell Assessment of NK Cell Cytotoxicity.
Guldevall K, Brandt L, Forslund E, Olofsson K, Frisk T, Olofsson P, et al
Front Immunol 2016 ;7():119

Dynamic Regulation of NK Cell Responsiveness.
Kadri N, Wagner A, Ganesan S, Kärre K, Wickström S, Johansson M, et al
Curr. Top. Microbiol. Immunol. 2016 ;395():95-114

         2015

Retuning of Mouse NK Cells after Interference with MHC Class I Sensing Adjusts Self-Tolerance but Preserves Anticancer Response.
Wagner A, Wickström S, Tallerico R, Salam S, Lakshmikanth T, Brauner H, et al
Cancer Immunol Res 2016 Feb;4(2):113-23

HLA class I downregulation is associated with enhanced NK-cell killing of melanoma cells with acquired drug resistance to BRAF inhibitors.
Sottile R, Pangigadde P, Tan T, Anichini A, Sabbatino F, Trecroci F, et al
Eur. J. Immunol. 2016 Feb;46(2):409-19

Depletion of IL-2 receptor β-positive cells protects from diabetes in non-obese diabetic mice.
Brauner H, Hall H, Flodström-Tullberg M, Kärre K, Höglund P, Johansson S
Immunol. Cell Biol. 2016 Feb;94(2):177-84

Enrichment of CD56(dim)KIR + CD57 + highly cytotoxic NK cells in tumour-infiltrated lymph nodes of melanoma patients.
Ali T, Pisanti S, Ciaglia E, Mortarini R, Anichini A, Garofalo C, et al
Nat Commun 2014 ;5():5639

         2014

A genetic defect in mice that impairs missing self recognition despite evidence for normal maturation and MHC class I-dependent education of NK cells.
Wickström S, Öberg L, Kärre K, Johansson M
J. Immunol. 2014 Feb;192(4):1577-86

        2013

Natural killer cell inhibitory receptor expression in humans and mice: a closer look.
Sternberg-Simon M, Brodin P, Pickman Y, Onfelt B, Kärre K, Malmberg K, et al
Front Immunol 2013 ;4():65

Human NK cells selective targeting of colon cancer-initiating cells: a role for natural cytotoxicity receptors and MHC class I molecules.
Tallerico R, Todaro M, Di Franco S, Maccalli C, Garofalo C, Sottile R, et al
J. Immunol. 2013 Mar;190(5):2381-90

        2012

Gut microbiota accelerate tumor growth via c-jun and STAT3 phosphorylation in APCMin/+ mice.
Li Y, Kundu P, Seow S, de Matos C, Aronsson L, Chin K, et al
Carcinogenesis 2012 Jun;33(6):1231-8

Expansion of T-cells from the cord blood graft as a predictive tool for complications and outcome of cord blood transplantation.
Gertow J, Berglund S, Okas M, Kärre K, Remberger M, Mattsson J, et al
Clin. Immunol. 2012 May;143(2):134-44

Skewing of the NK cell repertoire by MHC class I via quantitatively controlled enrichment and contraction of specific Ly49 subsets.
Brodin P, Lakshmikanth T, Kärre K, Höglund P
J. Immunol. 2012 Mar;188(5):2218-26

First International Meeting of the Thematic Centre for Immune Modulatory Therapies for Autoimmunity and Cancer (IMTAC) 13-14 June 2011, Ljusterö, Sweden.
Choudhury A, Höglund P, Kiessling R, Kärre K, Lundqvist A, Malmberg K, et al
Cancer Immunol. Immunother. 2012 Apr;61(4):587-91

Syntaxin 11 marks a distinct intracellular compartment recruited to the immunological synapse of NK cells to colocalize with cytotoxic granules.
Dabrazhynetskaya A, Ma J, Guerreiro-Cacais A, Arany Z, Rudd E, Henter J, et al
J. Cell. Mol. Med. 2012 Jan;16(1):129-41

Pharmacological activation of p53 triggers anticancer innate immune response through induction of ULBP2.
Li H, Lakshmikanth T, Garofalo C, Enge M, Spinnler C, Anichini A, et al
Cell Cycle 2011 Oct;10(19):3346-58

NK cell function and antibodies mediating ADCC in HIV-1-infected viremic and controller patients.
Johansson S, Rollman E, Chung A, Center R, Hejdeman B, Stratov I, et al
Viral Immunol. 2011 Oct;24(5):359-68

Syntaxin 11 marks a distinct intracellular compartment recruited to the immunological synapse of NK cells to colocalize with cytotoxic granules.
Dabrazhynetskaya A, Ma J, Guerreiro-Cacais A, Arany Z, Rudd E, Henter J, et al
J. Cell. Mol. Med. 2012 Jan;16(1):129-41

Increased cell-mediated immune responses in patients with recurrent herpes simplex virus type 2 meningitis.
Franzen-Röhl E, Schepis D, Lagrelius M, Franck K, Jones P, Liljeqvist J, et al
Clin. Vaccine Immunol. 2011 Apr;18(4):655-60

Publications 1976-2010

Publications 2003-2010 (pdf)

Publications 1976-2002 (Pdf file, 206 Kb)

Group Members

Professor

Klas Kärre

Phone: 08-524 862 82
Organizational unit: Klas Kärre group
E-mail: Klas.Karre@ki.se

Björn ÖnfeltAssociated
Ennio CarboneAssociated
Klas KärreProfessor
Maria JohanssonSenior researcher
Neha vashistAssociated
Rosa SottileGraduate Student
Sadia SalamPhD student, Graduate Student
Sofia JohanssonAssistant professor
Sunitha Bagawath singhPhD student, Graduate Student
Valentina CarannantePhD student, Graduate Student

Former Group Members

Former group members

Gallery

Common Room

Associates and Funding

Associates

Funding

Links

BD Fluorescence Spectrum Viewer

Immunology Journals (Impact factors according to ISI citation report)

Nature Immunology (28.2)
Immunity (16.0)
Journal of Experimental Medicine (15.3)
Journal of Clinical Investigation (14.3)
PNAS (10.3)
Blood (10.1)
Journal of Immunology (6.7)
European Journal of Immunology (4.5)
International Immunology (3.7)
Genes and Immunity (3.6)
Immunology (2.9)
Molecular Immunology (2.8)
Immunogenetics (2.7)
Human Immunology (2.6)
Scandinavian Journal of Immunology (1.9)
Immunobiology (1.8)

 

Immunology