IgG:Lma antigens binds FCGR3A:CD3 dimers

Stable Identifier
Reaction [binding]
Homo sapiens
Related Species
Leishmania major
Locations in the PathwayBrowser
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout
FCGRIII (CD16) is a low affinity Fc gamma receptor and is encoded by two genes (A and B), the transmembrane form FCGRIIIA and the GPI anchored FCGRIIIB (Edberg et al. 1989). FCGRIIIA is involved in phagocytosis and is expressed in macrophages and natural killer cells as a multi chain complex consisting of a single alpha chain containing IgG binding domains and a signal transducing gamma and/or zeta dimer (Wirthmuller et al. 1992, Lanier et al. 1989, Garcia Garcia & Rosales 2002). Both gamma and zeta chains contain a conserved immunoreceptor tyrosine based activation motif (ITAM), which has 2 copies of the YXXL sequence (Isakov 1997). However, the gamma chain of FCGRIIIA is approximately sixfold more efficient in mediating phagocytosis than the zeta subunit (Park & Schreiber 1995). Phosphorylation of the conserved tyrosine residues of the ITAM in these accessory proteins is required for the phagocytic signal mediated by FCRGIIIA.
The first step in Fc-gamma receptor (FCGR) phagocytosis is binding and clustering of FCGRs by IgG-coated foreign particles (For this particular pathway the coated foreing particle is the Leishmania parasite). FCGR are clustered at the cell surface by multivalent antigen-antibody complexes and recruited to lipid raft micro domains; monovalent ligand binding is insufficient to generate a signal.
This cross linking results in the localisation of FCGRs into lipid rafts and this may aid in their recruiting and complexing with additional signalling proteins associated with lipid rafts (Kono et al. 2002). This is followed by phosphorylation of the tyrosine residues within the ITAM located on the cytoplasmic portion of accessory gamma/zeta chains by membrane associated tyrosine kinases of the Src family (Park et al. 1993).
Literature References
PubMed ID Title Journal Year
2474607 Human Fc gamma RIII (CD16). Isoforms with distinct allelic expression, extracellular domains, and membrane linkages on polymorphonuclear and natural killer cells

Edberg, JC, Salmon, JE, Kimberly, RP, Redecha, PB

J Immunol 1989
1314888 Signal transduction by Fc gamma RIII (CD16) is mediated through the gamma chain

Wirthmueller, U, Ravetch, JV, Murakami, MS, Kurosaki, T

J Exp Med 1992
Event Information
Go Biological Process
Name Identifier Synonyms
cutaneous leishmaniasis DOID:9111 Asian Desert Cutaneous Leishmaniasis, Leproid leishmaniasis, diffuse cutaneous leishmaniasis
Cite Us!