The objective of the proposed research is to characterize a receptor for the Fc portion of IgG (termed CD16) that is expressed on the surface of human neutrophils. In previous work, I found that treatment of CD16 from neutrophils with N-glycanase yields two forms of the receptor. These forms differ with respect to their apparent molecular mass, primary structure, and reactivity with a monoclonal antibody (mAB) (GRAN-11) that recognizes CD16 on neutrophils from approximately 50% of normal individuals. These forms of neutrophil CD16 also differ with respect to their reactivity with alloantisera that recognize epitopes of the neutrophil-specific antigen (NA) system. Finally, I have identified a patient with SLE whose neutrophils express a form of CD16 that is altered with respect to its reactivity with a mAB (3G8) that recognizes CD16 on neutrophils from all normal individuals. The studies outline in this proposal are designed to reconcile the recently reported finding that CD16 is the product of a single gene with my own observations that there are polymorphic forms of CD16 on human neutrophils. Since I recently acquired a cDNA which encodes CD16 as well as a cDNA library prepared from human neutrophils, it should be possible to determine the molecular basis for the apparent polymorphism of CD16 on human neutrophils, as well as the molecular basis and functional consequences of an apparent abnormality of CD16 expression on neutrophils from a patient with SLE. Results of these studies should enhance our understanding of the pathogenesis of some rheumatic diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Clinical Investigator Award (CIA) (K08)
Project #
1K08AR001819-01
Application #
3079282
Study Section
Arthritis and Musculoskeletal and Skin Diseases Special Grants Review Committee (AMS)
Project Start
1989-07-01
Project End
1990-06-30
Budget Start
1989-07-01
Budget End
1990-06-30
Support Year
1
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143