A Novel Adaptor Protein Orchestrates Receptor Patterning and Cytoskeletal Polarity in T-Cell Contacts

Abstract

Recognition of antigen by T cells requires the formation of a specialized junction between the T cell and the antigen-presenting cell. This junction is generated by the recruitment and the exclusion of specific proteins from the contact area. The mechanisms that regulate these events are unknown. Here we demonstrate that ligand engagement of the adhesion molecule, CD2, initiates a process of protein segregation, CD2 clustering, and cytoskeletal polarization. Although protein segregation was not dependent on the cytoplasmic domain of CD2, CD2 clustering and cytoskeletal polarization required an interaction of the CD2 cytoplasmic domain with a novel SH3-containing protein. This novel protein, called CD2AP, is likely to facilitate receptor patterning in the contact area by linking specific adhesion receptors to the cytoskeleton.

A Large T Cell Invagination with CD2 Enrichment Resets Receptor Engagement in the Immunological Synapse

“…CD48iGFP thus reported CD2-driven accumulation of CD2/CD48 at the T cell-APC interface. Using human T cell clone-APC combinations or murine primary T cells on supported lipid bilayers as APC substitutes, accumulation of CD2/CD48 has previously been demonstrated, whether in a central pattern or spread over the interface (11,25).…”

Intercellular Trogocytosis Plays an Important Role in Modulation of Immune Responses

“…Subsequent (within minutes) to specific interactions of T cells with APCs, TCR and MHC molecules are assembled at the centre of supramolecular activation clusters at the site of T cell contact (2,(45)(46)(47). TCR-down-regulation is observed following interactions of TCR with pMHC complexes (48)(49)(50) and T cell-APC interactions cause APC-derived surface molecules to adhere to the surface of T cells (51,52).…”

Cloning and Characterization of a Novel Adaptor Protein, CIN85, That Interacts with c-Cbl

“…The proline-rich region contains multiple PXXP sequences which are possible SH3 domainbinding sites [49]. Further, it was revealed that CIN85 shares significant sequence identity with CMS [50] and CD2AP (a mouse homologue of CMS) [51], with overall 36 and 38% identity in amino acid sequence, respectively. The primary structures of these three proteins are also quite similar to one another.…”