Receptor ligand interactions in immune responses to cancer and viruses



Hugh Reyburn

Group Leader



Research summary

Current research in the laboratory addresses various issues related to the biology of NK cells and in particular the receptor NKG2D. We have a longstanding interest in studying the interactions between viruses and cells of the immune system as a strategy to gain insight into functionally important features of the immune system.




Bravo García-Morato M, Calvo Apalategi A, Bravo-Gallego LY, Blázquez Moreno A, Simón-Fuentes M, Garmendia JV, Méndez Echevarría A, Del Rosal Rabes T, Domínguez-Soto Á, López-Granados E, Reyburn HT, Rodríguez Pena R. Impaired control of multiple viral infections in a family with complete IRF9 deficiency J Allergy Clin Immunol. 2019 144:309-312.e10. doi: 10.1016/j.jaci.2019.02.019

Esteso G, Guerra S, Valés-Gómez M, Reyburn HT. Innate immune recognition of double-stranded RNA triggers increased expression of NKG2D ligands after virus infection. J Biol Chem. . 2017 292:20472-20480 doi: 10.1074/jbc.M117.818393

Blázquez-Moreno A, Pérez-Portilla A, Agúndez-Llaca M, Dukovska D, Valés-Gómez M, Aydogmus C, Ikinciogullari A, Regueiro JR, Reyburn HT. Analysis of the recovery of CD247 expression in a PID patient: insights into the spontaneous repair of defective genes.Analysis of the recovery of CD247 expression in a PID patient: insights into the spontaneous repair of defective genes. Blood. 2017 Sep 7;130(10):1205-1208.

Blázquez-Moreno A, Park S, Im W, Call MJ, Call ME, Reyburn HT. Transmembrane features governing Fc receptor CD16A assembly with CD16A signaling adaptor molecules. Proc Natl Acad Sci U S A. 2017 Jul 11;114(28):E5645-E5654.

Valés-Gómez M, Esteso G, Aydogmus C, Blázquez-Moreno A, Marín AV, Briones AC, Garcillán B, García-Cuesta EM, López Cobo S, Haskologlu S, Moraru M, Cipe F, Dobbs K, Dogu F, Parolini S, Notarangelo LD, Vilches C, Recio MJ, Regueiro JR, Ikinciogullari A, Reyburn HT. Natural killer cell hyporesponsiveness and impaired development in a CD247-deficient patient. J Allergy Clin Immunol 2016; 137:942-5


figuraReyburnNatural killer (NK) cells kill infected cells and secrete cytokines, to play an important role in defense against viral infection. Although NK cells are often perceived as rather primitive lymphocytes; always ready to kill unless checked by inhibitory receptors binding to MHC Class I molecules. It is now clear that the behaviour of an NK cell when confronted by a potential target cell depends on the integration of multiple signals coming from a range of activating and inhibitory receptors. Inhibitory receptor expression is largely under genetic control, whereas activation receptor expression is heavily environmentally influenced and NK cells adapt their expression of activating receptors in response to pathogens and tumours so giving rise to the multiple discrete NK cell subpopulations that can be found in human peripheral blood. Thus, to understand NK cells in disease requires detailed knowledge of the biochemistry of individual activating and inhibitory receptors and the subpopulations of NK cells expressing different receptor repertoires.

We have contributed extensively to knowledge of the cell biology of various NK cell receptors and their ligands and recently, to address the wider roles of NK cells in immunity, we have initiated collaborations with clinical colleagues to study patients suffering from primary immunodeficiencies that affect NK cell function. Inherited human immunodeficiencies are experiments of nature in which gene defects compromise immune function and our hypothesis is that the study of congenital defects affecting NK cells will help to increase our understanding of NK cell biology and function in vivo. We use innovative flow cytometry and molecular genetic technologies to characterise these primary immunodeficiency diseases at high resolution. These studies are complemented and enhanced by in vitro experiments involving the study of NK cells and the use of genome-editing technologies to study in detail the molecular bases of the changes observed in vivo.



Hugh Reyburn Principal investigator
Ane Calvo Apalategi Predoctoral scientist
Álvaro García Jiménez Predoctoral scientist
Daniel Fernández Soto Predoctoral scientist
Ruth Gómez-Caro Gil Technician

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