CD6 attenuates early and late signaling events, setting thresholds for T-cell activation.
Bottom Line: Measuring calcium mobilization in single cells responding to superantigen, we found that human T cells expressing rat CD6 react significantly less well compared with T cells not expressing the exogenous receptor.Calcium responses, and also late indicators of T-cell activation such as IL-2 release, were also diminished in TCR-activated Jurkat cells expressing human CD6, compared with CD6-deficient cells or cells expressing a cytoplasmic deletion mutant of human CD6.Our data suggest that CD6 is a signaling attenuator whose expression alone, i.e. in the absence of ligand engagement, is sufficient to restrain signaling in T cells.
Affiliation: Group of Cell Activation and Gene Expression, IBMC-Instituto de Biologia Molecular e Celular, Porto, Portugal.Show MeSH
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Mentions: Following transfection with a cDNA encoding rCD6 fused to YFP, the human T cells expressed variable levels of the chimeric protein (Fig. 1A, top panel). Endogenous human CD6 (hCD6) as well as human CD3 (hCD3) were highly expressed and their expression was unaffected by the coexpression of rCD6 (Fig. 1A, middle and bottom panels, respectively). Similarly, Raji cells (used as APCs) express human CD166 (hCD166), and so presumably in T cell–APC conjugates, T-cell surface hCD6 interacts with hCD166 expressed in Raji cells. We have considered untransfected T cells interacting with untransfected Raji the standard experimental setting, and changes that may occur following the expression of rCD6 and rCD166 should be due to specific functions of these heterologous rat molecules.
Affiliation: Group of Cell Activation and Gene Expression, IBMC-Instituto de Biologia Molecular e Celular, Porto, Portugal.