The role of CD99 in T cell activation, signaling, and immunological synapse formation

Abstract

Cytotoxic T lymphocytes (CTLs) provides a defense against virus-infected and tumorigenic cells. The recognition of antigen-presenting cells (APCs) for T cells and the association with them are essential in the formation of the immunological synapse (IS) which triggers T cell activation. Although various proteins that stabilize the IS structure for delivering appropriate signals in T cells have been identified, the role of adhesion molecule CD99 in CTL activation and IS formation has not been investigated. Here I found that CD99 in CTLs participates in T cell activation, proliferation, and effector differentiation by inducing of cluster formation between T cells and APCs. Interestingly, it is shown that CD99 is co-localized more at the peripheral supramolecular activating cluster (pSMAC) region than the central supramolecular activating cluster (cSMAC) in the IS, indicating the involvement of CD99 in IS formation. The absence of CD99 in CD8+ T cells resulted in slower formation of T-APC conjugates than WT CTLs. In addition, Akt-mediated signaling, followed by activation, proliferation, and cytokine production, was delayed in CD99KO CTLs upon TCR stimulation. Results presented here demonstrate for the first time that CD99 is recruited to the IS during APC and T cell interaction and plays an important role in subsequent T cell activation.