ICAM-1 inhibits the homocluster formation of MHC-I in colon carcinoma cells.
ICAM-1 and MHC-I proteins play fundamental roles in antigen presentation, activation of T lymphocytes, and immune responses against tumor cells. Both of them participate in the formation of lipid raft-associated membrane protein clusters. We found significant colocalization between ICAM-1 and MHC-I at the level of large-scale associations. We combined RNA interference and fluorescence resonance energy transfer studies to show that ICAM-1 promotes the partial disassembly of MHC-I homoclusters on LS-174T colon carcinoma cells. Interferon-gamma (IFN-gamma) treatment induced an increase in the expression of MHC-I and ICAM-1 resulting in decreased MHC-I homoassociation. Small interfering RNAs directed against ICAM-1 restored the homoassociation of MHC-I without influencing the expression level of MHC-I by eliminating ICAM-1 molecules interspersed in MHC-I clusters. We conclude that the composition of membrane protein clusters is dynamically altered in response to both physiological and experimentally elicited changes in antigen expression levels.
Nagy
Peter
P
Department of Biophysics and Cell Biology, Medical and Health Science Center, University of Debrecen, Hungary.
Vámosi
György
G
Damjanovich
Sándor
S
Damjanovich
László
L
D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics
D015395:Histocompatibility Antigens Class I; D034741:RNA, Small Interfering; D018799:Intercellular Adhesion Molecule-1