Recycling and LFA-1-dependent trafficking of ICAM-1 to the immunological synapse.
Little is known about how adhesion molecules on APCs accumulate at immunological synapses. We show here that ICAM-1 on APCs is continuously internalized and rapidly recycled back to the interface after antigen-priming T-cell contact. The internalization rate is high in APCs, including Raji B cells and dendritic cells, but low in endothelial cells. Internalization is significantly reduced by inhibitors of Na(+)/H(+) exchangers (NHEs), suggesting that members of the NHE-family regulate this process. Once internalized, ICAM-1 is co-localized with MHC class II in the polarized recycling compartment. Surprisingly, not only ICAM-1, but also MHC class II, is targeted to the immunological synapse through LFA-1-dependent adhesion. Cytosolic ICAM-1 is highly mobile and forms a tubular structure. Inhibitors of microtubule or actin polymerization can reduce ICAM-1 mobility, and thereby block accumulation at immunological synapses. Membrane ICAM-1 also moves to the T-cell contact zone, presumably through an active, cytoskeleton-dependent mechanism. Collectively, these results demonstrate that ICAM-1 can be transported to the immunological synapse through the recycling compartment. Furthermore, the high-affinity state of LFA-1 on T cells is critical to induce targeted movements of both ICAM-1 and MHC class II to the immunological synapse on APCs.
Jo
Jae-Hyeok
JH
School of Life Sciences, Cell Dynamics Research Center, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.
Kwon
Min-Sung
MS
Choi
Hyang-Ok
HO
Oh
Hyun-Mee
HM
Kim
Hyang-Jin
HJ
Jun
Chang-Duk
CD
D000938:Antigen-Presenting Cells / Q000276:immunology*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D004705:Endocytosis; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D054992:Immunological Synapses / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D021381:Protein Transport; D017923:Sodium-Hydrogen Exchangers; D013601:T-Lymphocytes / Q000276:immunology
D000949:Histocompatibility Antigens Class II; D016169:Lymphocyte Function-Associated Antigen-1; D017923:Sodium-Hydrogen Exchangers; D018799:Intercellular Adhesion Molecule-1