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PLoS One ; 7(11): e50396, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23226274

RESUMO

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.


Assuntos
Receptores de Antígenos de Linfócitos T gama-delta/genética , Transdução de Sinais/genética , Tetraspanina 28/genética , Animais , Antígenos CD5/genética , Antígenos CD5/imunologia , Comunicação Celular , Expressão Gênica , Células HEK293 , Humanos , Ativação Linfocitária , Camundongos , Camundongos Knockout , Plasmídeos , Ligação Proteica , RNA Interferente Pequeno/genética , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Transdução de Sinais/imunologia , Tetraspanina 28/antagonistas & inibidores , Tetraspanina 28/imunologia , Timócitos/citologia , Timócitos/metabolismo , Transfecção , Técnicas do Sistema de Duplo-Híbrido
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