Human immunodeficiency virus type-1 infection impairs the formation of the immunological synapse.
HIV-1-infected lymphocytes improperly respond to T cell antigen receptor (TCR) stimulation. To document this phenomenon, we studied the capacity of HIV-1-infected lymphocytes to form immunological synapses. We show here that HIV-1-infected T cells poorly conjugated with antigen-presenting cells, and when they formed conjugates, the synapses were abnormal. TCR and Lck accumulated in the recycling endosomal compartment, and their clustering at the synapse was severely reduced. These phenomena were, to a large extent, caused by Nef, a viral protein affecting intracellular trafficking and signaling pathways. Concomitantly, in HIV-infected cells, tyrosine phosphorylation at the synapse and the patterns of tyrosine phosphorylated proteins were disturbed in a Nef-dependent manner. These findings underscore the importance of Lck and TCR endosomal trafficking in synapse formation and early T cell signaling. Alteration of endocytic and signaling networks at the immunological synapse likely impacts the function and fate of HIV-1-infected cells.
Thoulouze
Maria Isabel
MI
Unité de Biologie Cellulaire des Lymphocytes, Centre National de la Recherche Scientifique Unité de Recherche Associée-1930, Institut Pasteur, 25-28 rue Dr Roux, 75724 Paris Cedex 15, France.
Sol-Foulon
Nathalie
N
Blanchet
Fabien
F
Dautry-Varsat
Alice
A
Schwartz
Olivier
O
Alcover
Andrés
A
D000938:Antigen-Presenting Cells / Q000276:immunology; D002450:Cell Communication / Q000276:immunology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015693:Gene Products, nef / Q000276:immunology / Q000378:metabolism*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000276:immunology; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000276:immunology / Q000378:metabolism; D018613:Microscopy, Confocal; D021381:Protein Transport / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D054311:nef Gene Products, Human Immunodeficiency Virus
D015693:Gene Products, nef; D011948:Receptors, Antigen, T-Cell; D054311:nef Gene Products, Human Immunodeficiency Virus; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)