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T Lymphocytes
Departments of
*
Immunology, and
Oncology and Signalisation dans les Cellules Hématopoïétiques, Unité 563, Institut National de la Santé et de la Recherche Médicale, Centre Hospitalier Universitaire de Purpan, Toulouse, France; and
Institut National de la Santé et de la Recherche Médicale, Unité 463, Nantes, France
Human T lymphocytes expressing the V
9V
2 TCR recognize non-peptidic Ags, referred to as phosphoantigens, produced by microbial pathogens and by human tumor cells. Here we show that T cells establish a mature immunological synapse (IS) with the myelomonocytic THP-1 tumoral cell line. This synapse is characterized by an enrichment for phosphotyrosine, CD2, and TCR together with the exclusion of CD45. The CD94 and NKG2D receptors are also recruited to the signaling area, while the C-lectin-like activation marker CD69 segregates out of the synapse. T cell conjugation to THP-1 increases upon stimulation by soluble phosphoantigen, is paralleled by the metabolic activation of T cells and leads to cytokine production. Molecular segregation of the above molecules also occurs at the T cell/THP-1 interface in the absence of exogenously added phosphoantigen, although it does not result in intracellular signaling and cytokine production under these conditions. Hence the molecular interactions at the T cell-THP-1 target cell interface are sufficient to induce the formation of an IS, but cytokine production requires the full engagement of TCR by a strong agonist. Thus in T cells, formation of the IS is uncoupled from its functional outcome.
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