title: Dual function of the NK cell receptor 2B4 (CD244) in the regulation of HCV-specific CD8+ T cells.
abstract: The outcome of viral infections is dependent on the function of CD8+ T cells which are tightly regulated by costimulatory molecules. The NK cell receptor 2B4 (CD244) is a transmembrane protein belonging to the Ig superfamily which can also be expressed by CD8+ T cells. The aim of this study was to analyze the role of 2B4 as an additional costimulatory receptor regulating CD8+ T cell function and in particular to investigate its implication for exhaustion of hepatitis C virus (HCV)-specific CD8+ T cells during persistent infection. We demonstrate that (i) 2B4 is expressed on virus-specific CD8+ T cells during acute and chronic hepatitis C, (ii) that 2B4 cross-linking can lead to both inhibition and activation of HCV-specific CD8+ T cell function, depending on expression levels of 2B4 and the intracellular adaptor molecule SAP and (iii) that 2B4 stimulation may counteract enhanced proliferation of HCV-specific CD8+ T cells induced by PD1 blockade. We suggest that 2B4 is another important molecule within the network of costimulatory/inhibitory receptors regulating CD8+ T cell function in acute and chronic hepatitis C and that 2B4 expression levels could also be a marker of CD8+ T cell dysfunction. Understanding in more detail how 2B4 exerts its differential effects could have implications for the development of novel immunotherapies of HCV infection aiming to achieve immune control.
authors.affiliation: Department for Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Schlaphoff
authors.forename: Sebastian
authors.initials: S
authors.lastname: Lunemann
authors.forename: Pothakamuri Venkata
authors.initials: PV
authors.lastname: Suneetha
authors.forename: Jerzy
authors.initials: J
authors.lastname: Jaroszewicz
authors.forename: Jan
authors.initials: J
authors.lastname: Grabowski
authors.forename: Julia
authors.initials: J
authors.lastname: Dietz
authors.forename: Fabian
authors.initials: F
authors.lastname: Helfritz
authors.forename: Hueseyin
authors.initials: H
authors.lastname: Bektas
authors.forename: Christoph
authors.initials: C
authors.lastname: Sarrazin
authors.forename: Michael Peter
authors.initials: MP
authors.lastname: Manns
authors.forename: Markus
authors.initials: M
authors.lastname: Cornberg
authors.forename: Heiner
authors.initials: H
authors.lastname: Wedemeyer
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D015415:Biomarkers; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D015870:Gene Expression; D016174:Hepacivirus / Q000276:immunology* / Q000378:metabolism; D019698:Hepatitis C, Chronic / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors / Q000276:immunology; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D000071176:Signaling Lymphocytic Activation Molecule Family
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; C084093:CD244 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D011971:Receptors, Immunologic; D000071176:Signaling Lymphocytic Activation Molecule Family