Tetraspanins are a family of membrane proteins that organize their molecular partners into signal transducing microdomains at the surface of eukaryotic cells. They are well known to regulate the migration and metastases of cancers. However, little is known about their role in immune cell migration. Here I show that two closely related tetraspanins, CD37 and CD82, have opposing roles in Dendritic cell migration and antigen presentation.
We have previously published that CD37-/- DC are hyperstimulatory to antigen-specific T cells, as CD37 negatively regulates peptide presentation by MHC. It is therefore surprising that cell mediated immunity in CD37-/- mice, in response to tumors and soluble antigens is poor. In vitro, in vivo and intravital analyses show that CD37 is essential for the optimal migration of dendritic cells from the periphery to draining lymph nodes. Similar defects in cell migration are also observed in CD37-/- neutrophils during inflammation.Investigations of the molecular mechanisms that underlie this poor migration point to defects in chemotaxis, integrin-mediated adhesion, and cytoskeletal dependent cell spreading and cell morphology.
Similarly to CD37-/- mice cell mediated immune responses are also poor in CD82-/- mice. However, here the underlying mechnisms are different as CD82-/- DC are poor presenters of antigen to T cells as antigen-pulsed CD82-/- DC have an inability to form stable conjugates with T cells. Also in contrast to CD37, CD82-/- DC show a hyper migratory phenotype in vitro and ex vivo assays. Analyses of adhesion to fibronectin point to a role for CD82 in regulating cytoskeletal-dependent cell spreading and a dysregulation of the GTPase Rho.