PROW: CD64

PROW and IWHLDA present the GUIDE on:
CD64
Authors: Paul Guyre; Wanwen Sun
Reviewer: Jan G. van de Winkel
[GUIDE BAR]

ALTERNATE NAMES FOR CD64

FC gammaRI
FCR I

MAJOR LINKS FOR CD64

NCBI LocusLink Record: 2209
Mendelian Inheritance in Man (OMIM): 146760
SwissProt annotated protein record: P12315
SwissProt annotated protein record: P12314

FUNCTION BIOCHEMICAL ACTIVITY OF CD64 - No information

CELLULAR FUNCTION OF CD64

Phagocytosis: Receptor-mediated endocytosis of IgG-antigen complexes
Antigen capture for presentation to T cells
Antibody-dependent cellular cytotoxicity
Release of cytokines and reactive oxygen intermediates

DISEASE RELEVANCE OF CD64 AND FUNCTION OF CD64 IN INTACT ANIMAL

Increased PMN expression associated with infectious diseases and therapy with
IFN[gamma] or G-CSF
CD64 protein is absent in one Belgian family with no marked disease consequences

STRUCTURE MOLECULAR FAMILY FOR CD64

Families in which CD64 is a member
- CD64-->Fc receptors for IgG
- CD64-->immunoglobulin supergene family

MOLECULAR STRUCTURE OF CD64

Three related genes, Fc[gamma]IA, IB and IC map to chromosome 1q21.1
The Fc[gamma]RIA gene product has 3 extracellular Ig-like domains
mAbs identified to date react only with the Fc[gamma]RIA gene product which has high affinity for IgG
Fc[gamma]RIA-encoded protein is expressed as a multi-subunit receptor; requires association with [gamma]:[gamma] homodimer ([gamma] chain of IgE receptor) to mediate phagocytosis

MOLECULAR MASS OF CD64

CELL TYPE	MW UNREDUCED	MW REDUCED	Comment
Monocytes		72 kDa
U937, HL-60		72 kDa

POST-TRANSCRIPTIONAL MODIFICATION OF CD64

Fc[gamma]RIB has alternative splice sites yielding Fc[gamma]RIb1 and 1b2

POST-TRANSLATIONAL MODIFICATION OF CD64

Fc[gamma]RIA-encoded protein is highly glycosylated; IB and IC genes encode
glycosylation sites but proteins have not been characterized

MOLECULAR INTERACTIONS PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD64

MOLECULE	COMMENT
STAT1	IFN[gamma] induces increased transcription of CD64 in PMN via STAT1 and STAT3 binding to the IFN[gamma] response region (GRR)
STAT3	IFN[gamma] induces increased transcription of CD64 in PMN via STAT1 and STAT3 binding to the IFN[gamma] response region (GRR)
unknown	Increased expression in monocytes and macrophages by IFN-[gamma] and IL-10
Unkonwn	Decreased expression in monocytes and macrophages by IL-4
Unknown	Decreased expression in PMN by glucocorticoids

SUBSTRATES FOR CD64 - No information

ENZYMES WHICH MODIFY CD64 - No information

LIGANDS FOR CD64 AND MOLECULES ASSOCIATED WITH CD64

MOLECULE	COMMENT
IgG human	Human CD64 binds human IgG3>IgG1>IgG4>>>IgG2
IgG mouse	Human CD64 binds murine IgG3>IgG2a>>>IgG1, IgG2b

EXPRESSION MAIN CELLULAR EXPRESSION OF CD64

Monocytes
Macrophages
Blood dendritic cell subset and germinal center dendritic cells
Monocytes, macrophages
PMN activated by IFN-[gamma] or G-CSF
Expressed also on early myeloid lineage cells

AUTHOR'S ADDITIONAL INSIGHTS ON CD64

PE-CY5 Tandem conjugates bind specifically to CD64 leading to high background staining of CD64 positive cells

REAGENTS CD64-SPECIFIC MABS NEWLY ASSIGNED AT SIXTH INTERNATIONAL WORKSHOP - No information

SELECTION OF OTHER CD64-SPECIFIC REFERENCE MAB

NAME(Workshop IDs)	SOURCE or REFERENCE	COMMENT
22	Guyre PM et al. 1989
32	Anderson CL et al. 1986
197	Guyre PM et al. 1989
10.1	Dougherty GJ 1987

SELECTED REFERENCES ON CD64

REVIEWS

1. Hulett MD,Hogarth PM Molecular basis of Fc receptor function. Adv Immunol 1994 57:1 PubMed

2. Van de Winkel, J.G.J & Capel, P.J.A. [Editors]. Human IgG Fc Receptors. R.G. Landes Company, Austin, TX, USA, 1996.

3. van de Winkel JG,Capel PJ Human IgG Fc receptor heterogeneity: molecular aspects and clinical implications. Immunol Today 1993 14:215 PubMed

PRIMARY CITATIONS

4. Anderson CL,Guyre PM,Whitin JC,Ryan DH,Looney RJ,Fanger MW Monoclonal antibodies to Fc receptors for IgG on human mononuclear phagocytes. Antibody characterization and induction of superoxide production in a monocyte cell line. J Biol Chem 1986 261:12856 PubMed

5. Dougherty GJ,Selvendran Y,Murdoch S,Palmer DG,Hogg N The human mononuclear phagocyte high-affinity Fc receptor, FcRI, defined by a monoclonal antibody, 10.1. Eur J Immunol 1987 17:1453 PubMed

6. Fanger NA,Wardwell K,Shen L,Tedder TF,Guyre PM Type I (CD64) and type II (CD32) Fc gamma receptor-mediated phagocytosis by human blood dendritic cells. J Immunol 1996 157:541 PubMed

7. Olweus J,Terstappen LW,Thompson PA,Lund-Johansen F Expression and function of receptors for stem cell factor and erythropoietin during lineage commitment of human hematopoietic progenitor cells. Blood 1996 88:1594 PubMed

8. van Vugt MJ,Heijnen AF,Capel PJ,Park SY,Ra C,Saito T,Verbeek JS,van de Winkel JG FcR gamma-chain is essential for both surface expression and function of human Fc gamma RI (CD64) in vivo. Blood 1996 87:3593 PubMed

9. van Vugt MJ,van den Herik-Oudijk IE,van de Winkle JG Binding of PE-CY5 conjugates to the human high-affinity receptor for IgG. Blood 1996 88:2358 PubMed

WWW RESOURCES

* indicates ammended by reviewer, ** indicates added by reviewer

Portions copyright by Garland Press and by the International Workshops on Human Leukocyte Differentiation Antigens; used with permission

Modified 10/14/99 mpr@mail.nih.gov