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      Cd81 Interacts with the T Cell Receptor to Suppress Signaling

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      Author
      Cevik, S.I.
      Keskin, N.
      Belkaya, S.
      Ozlu, M.I.
      Deniz, E.
      Tazebay, U.H.
      Erman, B.
      Date
      2012
      Source Title
      PLoS ONE
      Print ISSN
      19326203
      Volume
      7
      Issue
      11
      Language
      English
      Type
      Article
      Item Usage Stats
      141
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      127
      downloads
      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. © 2012 Cevik et al.
      Keywords
      CD3 antigen
      CD5 antigen
      CD81 antigen
      short hairpin RNA
      T lymphocyte receptor
      T lymphocyte receptor delta chain
      antigen function
      article
      cell maturation
      controlled study
      gene rearrangement
      gene silencing
      human
      human cell
      immunoregulation
      intracellular signaling
      lymphocyte differentiation
      lymphocyte proliferation
      nucleotide sequence
      protein determination
      protein expression
      protein protein interaction
      thymocyte
      two hybrid system
      Animals
      Antigens, CD5
      Antigens, CD81
      Cell Communication
      Gene Expression
      HEK293 Cells
      Humans
      Lymphocyte Activation
      Mice
      Mice, Knockout
      Plasmids
      Protein Binding
      Receptors, Antigen, T-Cell, gamma-delta
      RNA, Small Interfering
      Signal Transduction
      Thymocytes
      Transfection
      Two-Hybrid System Techniques
      Hepatitis C virus
      Mus
      Permalink
      http://hdl.handle.net/11693/21250
      Published Version (Please cite this version)
      http://dx.doi.org/10.1371/journal.pone.0050396
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      • Department of Molecular Biology and Genetics 426
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