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: We addressed the role of the cytoplasmic domain of CD6 using an engineered isoform of rCD6 lacking its cytoplasmic domain, rCD6CY5 fused to YFP, which was expressed in ex vivo human T cells. rCD6CY5 moved to the synapse when the T cells were allowed to form conjugates with rCD166-expressing Raji cells (data not shown). Calcium signals were measured in individual cells conjugated with rCD166+ Raji cells, and we found that the fraction of T cells expressing rCD6CY5 that increased their calcium levels following conjugate formation (i.e. ∼66%; Fig. 4A) closely matched that of rCD6− cells (Fig. 1C). For the responding T cells expressing rCD6CY5 (n=10), we measured calcium signals and compared these with signals from responding T cells expressing full-length rCD6 (n=15; Fig. 4B and Supporting Information Fig. 2). The results indicate that rCD6-expressing cells displayed lower and more transient calcium signals than cells expressing rCD6CY5, and thus the inhibitory effects of CD6 can be assigned to its cytoplasmic tail.
Affiliation: Group of Cell Activation and Gene Expression, IBMC-Instituto de Biologia Molecular e Celular, Porto, Portugal.