title: Modulation of natural killer cell functions by interactions between 2B4 and CD48 in cis and in trans.
abstract: SLAM-related receptors (SRRs) are important modulators of immune cell function. While most SRRs are homophilic, 2B4 (CD244) interacts with CD48, a GPI-anchored protein expressed on many haematopoietic cells. Here we show that natural killer (NK) cell-expressed 2B4 not only binds in trans to CD48 on neighbouring cells but also interacts in cis with CD48 on the same cell. 2B4 uses the same binding site to interact with CD48 in cis and in trans and structural flexibility of 2B4 is necessary for the cis interaction. Furthermore, the cis interaction is sufficient to induce basal phosphorylation of 2B4. However, cis interaction reduces the ability of 2B4 to bind CD48 in trans As a consequence, stimulation-dependent phosphorylation of 2B4 upon binding to CD48 positive target cells is reduced. Interfering with the cis interaction therefore enhanced the lysis of CD48-expressing tumour cells. These data show that the density of 2B4 and CD48 on both the NK cell and the potential target cell modulates NK cell activity.
authors.affiliation: Leibniz Research Centre for Working Environment and Human Factors at TU Dortmund (IfADo) Dortmund, Germany.
authors.forename: Maren
authors.initials: M
authors.lastname: Claus
authors.affiliation: Leibniz Research Centre for Working Environment and Human Factors at TU Dortmund (IfADo) Dortmund, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Wingert
authors.affiliation: Leibniz Research Centre for Working Environment and Human Factors at TU Dortmund (IfADo) Dortmund, Germany watzl@ifado.de.
authors.forename: Carsten
authors.identifier: 0000-0001-5195-0995
authors.initials: C
authors.lastname: Watzl
mesh_terms: D001665:Binding Sites; D000071178:CD48 Antigen / Q000737:chemistry / Q000378:metabolism*; D018920:Coculture Techniques; D057809:HEK293 Cells; D006801:Humans; D019169:Jurkat Cells; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology; D010766:Phosphorylation; D011485:Protein Binding; D000071176:Signaling Lymphocytic Activation Molecule Family / Q000737:chemistry / Q000378:metabolism*
chemical_list: C084093:CD244 protein, human; D000071178:CD48 Antigen; C000604065:CD48 protein, human; D000071176:Signaling Lymphocytic Activation Molecule Family
keywords: 2B4; CD48; cytotoxicity; natural killer cells; surface receptors