title: The Reorientation of T-Cell Polarity and Inhibition of Immunological Synapse Formation by CD46 Involves Its Recruitment to Lipid Rafts.
abstract: Many infectious agents utilize CD46 for infection of human cells, and therapeutic applications of CD46-binding viruses are now being explored. Besides mediating internalization to enable infection, binding to CD46 can directly alter immune function. In particular, ligation of CD46 by antibodies or by measles virus can prevent activation of T cells by altering T-cell polarity and consequently preventing the formation of an immunological synapse. Here, we define a mechanism by which CD46 reorients T-cell polarity to prevent T-cell receptor signaling in response to antigen presentation. We show that CD46 associates with lipid rafts upon ligation, and that this reduces recruitment of both lipid rafts and the microtubule organizing centre to the site of receptor cross-linking. These data combined indicate that polarization of T cells towards the site of CD46 ligation prevents formation of an immunological synapse, and this is associated with the ability of CD46 to recruit lipid rafts away from the site of TCR ligation.
authors.affiliation: Peter MacCallum Cancer Centre, East Melbourne, VIC 3002, Australia.
authors.forename: Mandy J
authors.initials: MJ
authors.lastname: Ludford-Menting
authors.forename: Blessing
authors.initials: B
authors.lastname: Crimeen-Irwin
authors.forename: Jane
authors.initials: J
authors.lastname: Oliaro
authors.forename: Anupama
authors.initials: A
authors.lastname: Pasam
authors.forename: David
authors.initials: D
authors.lastname: Williamson
authors.forename: Natalie
authors.initials: N
authors.lastname: Pedersen
authors.forename: Patricia
authors.initials: P
authors.lastname: Guillaumot
authors.forename: Dale
authors.initials: D
authors.lastname: Christansen
authors.forename: Serge
authors.initials: S
authors.lastname: Manie
authors.forename: Katharina
authors.initials: K
authors.lastname: Gaus
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Russell