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This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by van Vugt, M. J. Articles by van de Winkel, J. G.J. Search for Related Content PubMed PubMed Citation Articles by van Vugt, M. J. Articles by van de Winkel, J. G.J. Related Collections Phagocytes Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, Vol. 94 No. 2 (July 15), 1999: pp. 808-817 The FcRIa (CD64) Ligand Binding Chain Triggers Major Histocompatibility Complex Class II Antigen Presentation Independently of Its Associated FcR -Chain Martine J. van Vugt, Monique J. Kleijmeer, Tibor Keler, Ingrid Zeelenberg, Marc A. van Dijk, Jeanette H.W. Leusen, Hans J. Geuze, and Jan G.J. van de Winkel From the Departments of Immunology and Cell Biology, and Medarex Europe University Hospital Utrecht, Utrecht, The Netherlands; and Medarex, Annandale, NJ. Within multi-subunit Ig receptors, the FcR -chain immunoreceptor tyrosine-based activation motif (ITAM) plays a crucial role in enabling antigen presentation. This process involves antigen-capture and targeting to specific degradation and major histocompatibility complex (MHC) class II loading compartments. Antigenic epitopes are then presented by MHC class II molecules to specific T cells. The high-affinity receptor for IgG, hFcRIa, is exclusively expressed on myeloid lineage cells and depends on the FcR -chain for surface expression, efficient ligand binding, and most phagocytic effector functions. However, we show in this report, using the IIA1.6 cell model, that hFcRIa can potentiate MHC class II antigen presentation, independently of a functional FcR -chain ITAM. Immunoelectron microscopic analyses documented hFcRIa -chain/rabbit IgG-Ovalbumin complexes to be internalized and to migrate via sorting endosomes to MHC class II-containing late endosomes. Radical deletion of the hFcRIa -chain cytoplasmic tail did not affect internalization of rabbit IgG-Ovalbumin complexes. Importantly, however, this resulted in diversion of receptor-ligand complexes to the recycling pathway and decreased antigen presentation. These results show the hFcRIa cytoplasmic tail to contain autonomous targeting information for intracellular trafficking of receptor-antigen complexes, although deficient in canonical tyrosine- or dileucine-targeting motifs. This is the first documentation of autonomous targeting by a member of the multichain FcR family that may critically impact the immunoregulatory role proposed for hFcRIa (CD64). CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: X. Li, K. Su, C. Ji, A. J. Szalai, J. Wu, Y. Zhang, T. Zhou, R. P. Kimberly, and J. C. Edberg Immune Opsonins Modulate BLyS/BAFF Release in a Receptor-Specific Fashion J. Immunol., July 15, 2008; 181(2): 1012 - 1018. [Abstract] [Full Text] [PDF] J. M. Beekman, C. E. van der Poel, J. A. van der Linden, D. L. C. van den Berg, P. V. E. van den Berghe, J. G. J. van de Winkel, and J. H. W. Leusen Filamin A Stabilizes Fc{gamma}RI Surface Expression and Prevents Its Lysosomal Routing J. Immunol., March 15, 2008; 180(6): 3938 - 3945. [Abstract] [Full Text] [PDF] L.-Z. He, A. Crocker, J. Lee, J. Mendoza-Ramirez, X.-T. Wang, L. A. Vitale, T. O'Neill, C. Petromilli, H.-F. Zhang, J. 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