Ligation of the cell surface receptor, CD46, alters T cell polarity and response to antigen presentation.
Lymphocyte function in vivo is dictated by multiple external cues, but the integration of different signals is not well understood. Here, we show that competition for the axis of polarization dictates functional outcomes. We investigated the effect of ligation of the immunoregulatory cell surface receptor, CD46, on lymphocyte polarity during antigen presentation and cytotoxic effector function. Ligation of CD46 on human T cells prevented recruitment of the microtubule organizing center, CD3, and perforin to the interface with the antigen-presenting cell and caused a reduction in IFN-gamma production. In human NK cells, similar changes in polarity induced by CD46 ligation inhibited the recruitment of the microtubule organizing center and perforin to the interface with target cells and correlated with reduced killing. These data indicate that external signals can alter lymphocyte polarization toward antigen-presenting cells or target cells, inhibiting lymphocyte function.
Oliaro
Jane
J
Immune Signalling Laboratory, Peter MacCallum Cancer Centre, Faculty of Medicine, University of Melbourne, St. Andrew's Place, East Melbourne, VIC 3010, Australia.
Pasam
Anupama
A
Waterhouse
Nigel J
NJ
Browne
Kylie A
KA
Ludford-Menting
Mandy J
MJ
Trapani
Joseph A
JA
Russell
Sarah M
SM
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D017252:CD3 Complex / Q000378:metabolism; D016764:Cell Polarity / Q000276:immunology*; D002478:Cells, Cultured; D006367:HeLa Cells; D006801:Humans; D007106:Immune Sera / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000378:metabolism; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D007739:L Cells; D008024:Ligands; D051916:Membrane Cofactor Protein / Q000276:immunology / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D051379:Mice; D022101:Microtubule-Organizing Center / Q000378:metabolism; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*
D017252:CD3 Complex; C497857:CD46 protein, human; D007106:Immune Sera; D007166:Immunosuppressive Agents; D008024:Ligands; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; D007371:Interferon-gamma