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-γ (IFN-γ) 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.