Björn Önfelt Project

The primary focus of our research is to understand the processes in which Natural Killer cells (NK cells) and T-cells communicate with and eliminate cells that are potentially harmful to the body.

Picture describes Natural Killer cells (NK cells) and membrano nanotypes

Project description

The heterogeneity regarding the receptor expression patterns and effector functions of the target cell populations makes these phenomena utterly complex. Most immunological setups in this field focus on readouts based on the average of the cell population. Thus far we have pursued the goal of developing new assays that can be used in academic research as well as the pharmaceutical and health care industry. We focus on approaches that provide the means to study the behavior of single cells and small subpopulations of cells. In the future this will enable us to effectively study how individual NK cells respond to different conditions.

Cell mediated immunity by NK cells is achieved by the formation of an immune synapse. This is a highly organized sub cellular interface between the NK cell and the target cell involving a number of communication processes leading to secretion of cytotoxic molecules and killing of the target cell. To address heterogeneity of NK cell populations we have developed two microchip-based approaches for high resolution imaging of individual NK cells or NK cell-target-cell conjugates over extended periods of time. The cells are restricted in space by miniature wells organized in an array format or an ultrasonic cage, which promotes and facilitates studies of cell-cell interactions.

In order to characterize the intermittent movements of lymphocytes we implement a method that has previously been used in single molecule tracking studies. That makes it possible to automatically detect and quantify the periods of transient migration arrest that is typical for these cells. The method allows quick assessment and quantification of altered migration properties of cells during e.g. drug treatments and infections.

Group Members

  • Bruno Vanherberghen, Postdoc, Cell Physics, Royal Institute of Technology
  • Thomas Frisk, Postdoc, MTC Karolinska Institute and Cell Physics, Royal Institute of Technology
  • Karolin Guldevall, PhD student, Cell Physics, Royal Institute of Technology
  • Ali Khorshidi, PhD student, Cell Physics, Royal Institute of Technology

Selected Publications

Human NK Cells Lyse Th2-Polarizing Dendritic Cells via NKp30 and DNAM-1.
Walwyn-Brown K, Guldevall K, Saeed M, Pende D, Önfelt B, MacDonald AS, et al
J Immunol 2018 10;201(7):2028-2041

Shedding of CD16 disassembles the NK cell immune synapse and boosts serial engagement of target cells.
Srpan K, Ambrose A, Karampatzakis A, Saeed M, Cartwright ANR, Guldevall K, et al
J Cell Biol 2018 09;217(9):3267-3283

161533 TriKE stimulates NK-cell function to overcome myeloid-derived suppressor cells in MDS.
Sarhan D, Brandt L, Felices M, Guldevall K, Lenvik T, Hinderlie P, et al
Blood Adv 2018 06;2(12):1459-1469

Intrinsic Functional Potential of NK-Cell Subsets Constrains Retargeting Driven by Chimeric Antigen Receptors.
Oei VYS, Siernicka M, Graczyk-Jarzynka A, Hoel HJ, Yang W, Palacios D, et al
Cancer Immunol Res 2018 04;6(4):467-480

NK cells converge lytic granules to promote cytotoxicity and prevent bystander killing.
Hsu HT, Mace EM, Carisey AF, Viswanath DI, Christakou AE, Wiklund M, et al
J Cell Biol 2016 Dec;215(6):875-889

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

Microchip-Based Single-Cell Imaging Reveals That CD56dimCD57-KIR-NKG2A+ NK Cells Have More Dynamic Migration Associated with Increased Target Cell Conjugation and Probability of Killing Compared to CD56dimCD57-KIR-NKG2A- NK Cells.
Forslund E, Sohlberg E, Enqvist M, Olofsson PE, Malmberg KJ, Önfelt B
J Immunol 2015 Oct;195(7):3374-81

Ultrasonic three-dimensional on-chip cell culture for dynamic studies of tumor immune surveillance by natural killer cells.
Christakou AE, Ohlin M, Önfelt B, Wiklund M
Lab Chip 2015 Aug;15(15):3222-31

Single-Cell Characterization of in vitro Migration and Interaction Dynamics of T Cells Expanded with IL-2 and IL-7.
Tauriainen J, Gustafsson K, Göthlin M, Gertow J, Buggert M, Frisk TW, et al
Front Immunol 2015 ;6():196

Coordinated expression of DNAM-1 and LFA-1 in educated NK cells.
Enqvist M, Ask EH, Forslund E, Carlsten M, Abrahamsen G, Béziat V, et al
J Immunol 2015 May;194(9):4518-27

Single-Cell Characterization of in vitro Migration and Interaction Dynamics of T Cells Expanded with IL-2 and IL-7.
Tauriainen J, Gustafsson K, Göthlin M, Gertow J, Buggert M, Frisk TW, et al
Front Immunol 2015 ;6():196

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 KJ, et al
Front Immunol 2013 ;4():65

Live cell imaging in a micro-array of acoustic traps facilitates quantification of natural killer cell heterogeneity.
Christakou AE, Ohlin M, Vanherberghen B, Khorshidi MA, Kadri N, Frisk T, et al
Integr Biol (Camb) 2013 Apr;5(4):712-9

Classification of human natural killer cells based on migration behavior and cytotoxic response.
Vanherberghen B, Olofsson PE, Forslund E, Sternberg-Simon M, Khorshidi MA, Pacouret S, et al
Blood 2013 Feb;121(8):1326-34

Visualization of custom-tailored iron oxide nanoparticles chemistry, uptake, and toxicity.
Wilkinson K, Ekstrand-Hammarström B, Ahlinder L, Guldevall K, Pazik R, Kępiński L, et al
Nanoscale 2012 Dec;4(23):7383-93

Novel Microchip-Based Tools Facilitating Live Cell Imaging and Assessment of Functional Heterogeneity within NK Cell Populations.
Forslund E, Guldevall K, Olofsson PE, Frisk T, Christakou AE, Wiklund M, et al
Front Immunol 2012 ;3():300

Plekhh2, a novel podocyte protein downregulated in human focal segmental glomerulosclerosis, is involved in matrix adhesion and actin dynamics.
Perisic L, Lal M, Hulkko J, Hultenby K, Önfelt B, Sun Y, et al
Kidney Int 2012 Nov;82(10):1071-83

A silicon-glass microwell platform for high-resolution imaging and high-content screening with single cell resolution.
Frisk TW, Khorshidi MA, Guldevall K, Vanherberghen B, Önfelt B
Biomed Microdevices 2011 Aug;13(4):683-93

Analysis of transient migration behavior of natural killer cells imaged in situ and in vitro.
Khorshidi MA, Vanherberghen B, Kowalewski JM, Garrod KR, Lindström S, Andersson-Svahn H, et al Integr Biol (Camb) 2011 Jul;3(7):770-8

Live cell linear dichroism imaging reveals extensive membrane ruffling within the docking structure of natural killer cell immune synapses.
Benninger RK, Vanherberghen B, Young S, Taner SB, Culley FJ, Schnyder T, et al
Biophys J 2009 Jan;96(2):L13-5

Flow-free transport of cells in microchannels by frequency-modulated ultrasound.
Manneberg O, Vanherberghen B, Onfelt B, Wiklund M
Lab Chip 2009 Mar;9(6):833-7

Membrane nanotubes physically connect T cells over long distances presenting a novel route for HIV-1 transmission.
Sowinski S, Jolly C, Berninghausen O, Purbhoo MA, Chauveau A, Köhler K, et al
Nat Cell Biol 2008 Feb;10(2):211-9


Björn Önfelt

Affiliated to research
C1 Department of Microbiology, Tumor and Cell Biology