title: CD81 interacts with the T cell receptor to suppress signaling.
abstract: CD81 (TAPA-1) is a ubiquitously expressed tetraspanin protein identified as a component of the B lymphocyte receptor (BCR) and as a receptor for the Hepatitis C Virus. In an effort to identify trans-membrane proteins that interact with the T-cell antigen receptor (TCR), we performed a membrane yeast two hybrid screen and identified CD81 as an interactor of the CD3delta subunit of the TCR. We found that in the absence of CD81, in thymocytes from knockout mice, TCR engagement resulted in stronger signals. These results were recapitulated in T cell lines that express low levels of CD81 through shRNA mediated silencing. Increased signaling did not result from alterations in the levels of TCR on the surface of T lymphocytes. Although CD81 is not essential for normal T lymphocyte development, it plays an important role in regulating TCR and possibly pre-TCR signal transduction by controlling the strength of signaling. CD81 dependent alterations in thymocyte signaling are evident in increased CD5 expression on CD81 deficient double positive (DP) thymocytes. We conclude that CD81 interacts with the T cell receptor to suppress signaling.
authors.affiliation: Biological Sciences and Bioengineering Program, Faculty of Engineering and Natural Sciences, Sabanci University, Istanbul, Turkey.
authors.forename: Safak Isil
authors.initials: SI
authors.lastname: Cevik
authors.forename: Nazli
authors.initials: N
authors.lastname: Keskin
authors.forename: Serkan
authors.initials: S
authors.lastname: Belkaya
authors.forename: Meral Ilcim
authors.initials: MI
authors.lastname: Ozlu
authors.forename: Emre
authors.initials: E
authors.lastname: Deniz
authors.forename: Uygar Halis
authors.initials: UH
authors.lastname: Tazebay
authors.forename: Batu
authors.initials: B
authors.lastname: Erman
mesh_terms: D000818:Animals; D018956:CD5 Antigens / Q000235:genetics / Q000276:immunology; D002450:Cell Communication; D015870:Gene Expression; D057809:HEK293 Cells; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D010957:Plasmids; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics* / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics* / Q000276:immunology; D060225:Tetraspanin 28 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology; D060168:Thymocytes / Q000166:cytology / Q000378:metabolism; D014162:Transfection; D020798:Two-Hybrid System Techniques
chemical_list: D018956:CD5 Antigens; D034741:RNA, Small Interfering; D016692:Receptors, Antigen, T-Cell, gamma-delta; D060225:Tetraspanin 28