Cutting Edge: Dynamic Redistribution of Tetraspanin CD81 at the Central Zone of the Immune Synapse in Both T Lymphocytes and APC

Abstract

The tetraspanin CD81 has been involved in T-dependent B cell-mediated immune responses. However, the behavior of CD81 during immune synapse (IS) formation has not been elucidated. We determined herein that CD81 redistributed to the contact area of T cell-B cell and T cell-dendritic cell conjugates in an Ag-dependent manner. Confocal microscopy showed that CD81 colocalized with CD3 at the central supramolecular activation complex. Videomicroscopy studies with APC or T cells transiently expressing CD81-green fluorescent protein (GFP) revealed that in both cells CD81 redistributed toward the central supramolecular activation complex. In T lymphocytes, CD81-GFP rapidly redistributed to the IS, whereas, in the APC, CD81-GFP formed a large accumulation in the contact area that later concentrated in a discrete cluster and waves of CD81 accumulated at the IS periphery. These results suggest a relevant role for CD81 in the topography of the IS that would explain its functional implication in T cell-B cell collaboration.

SCIMP, a Transmembrane Adaptor Protein Involved in Major Histocompatibility Complex Class II Signaling

“…MHC-II molecules loaded with specific antigenic peptides appear to be enriched in TEMs (30,47), and it has been suggested that TEMs might increase the chance of successful presentation of a limited pool of MHC-II molecules loaded with specific peptides. This would be in agreement with the observation that tetraspanins are constituents of IS (34). SCIMP is also rapidly translocated to IS.…”

“…Thus far, we have demonstrated that SCIMP is a part of MHC-II-containing TEMs. Some of the tetraspanins have been shown to partition to the IS between the APC and the T cell (34). To find out whether SCIMP may also localize to the IS, we used Ramos and Daudi B cell lines expressing SCIMP-GFP as APCs in a superantigen staphylococcal enterotoxin E (SEE)-based assay.…”

Association of CD26 with CD45RA outside lipid rafts attenuates cord blood T-cell activation

“…35,36 We have demonstrated that CD26 is costimulatory for CD3-induced signal transduction and targeting of CD26 to lipid rafts is necessary for signaling events through CD26. 16 We first investigated whether disruption of lipid rafts' integrity via cholesterol extraction with M␤CD would inhibit CD26-induced signal transduction.…”

Complementary costimulation of human T-cell subpopulations by cluster of differentiation 28 (CD28) and CD81

“…Tetraspanins play a role in membrane fusion, cell migration, and in signal transduction (29)(30)(31)(32). The role of CD81 as a costimulatory molecule is of special interest because it has been shown to localize at the site of interaction between B cells and T cells in a central supermolecular cluster (33).…”