Human Immunodeficiency Virus Type-1 infection Impairs the Formation of the immunological Synapse

Speaker: 蔡明勳                    Time: 13:00-14:00, 12/13, 2006

Commentator: 陳舜華 老師           Place: Room 601

Abstract

Immunological synapses are thought to constitute in time and space the complex communication between the T lymphocyte and the antigen presenting cell (APC), for providing efficient TCR-MHC-antigen recognition, T cell activation, and stimulation signals to the APC. Although HIV-infected cells showed alterations in signaling pathway and intracellular protein trafficking, little is know about the consequences of HIV infection on the formation of the immunological synapse. In this paper, the authors showed that HIV-1 infected T cells conjugated with APC poorly, and reduced TCR as well as Lck, the first tyrosine kinase activated after TCR engagement, clustering at the synapses. By using wild-type and Nef-defective HIV-1, they demonstrated that Nef protein interfered with Lck targeting to immunological synapse and induced Lck endosomal retention. Moreover, by using lentiviral vector encoding Nef-wt or inactive Nef mutant (Nef-G2A), they foundNef protein alone was sufficient to disrupt Lck localization and immunological synapse formation, and these effects were independent on Nef-induced CD4 and CD28 downregulation. In addition, By PdBu(phorbol 12,13-dibutyrate) -induced TCR internalization, they found HIV-1 Nef also affected TCR trafficking and delayed TCR endocytosis. As a result, TCR accumulated in recyclingendosomes in HIV-1-infected T cells. Furthermore, HIV-1 infection blocked early tyrosine-phosphorylation signaling at the immunological synapse. Taken together, the results of this study indicate that HIV-1 might prevent T cells activation and immunological synapse formation by HIV-1 Nef protein, disrupt TCR early phosphorylation events, and intracellular trafficking.

Reference

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3.          Thoulouze, M.I., Sol-Foulon, N., Blanchet, F., Dautry-Varsat, A., Schwartz, O., and Alcover, A. (2006). Human immunodeficiency virus type-1 infection impairs the formation of the immunological synapse. Immunity 24: 547-561.