Adhesion to the external environment is essential to both T cell migration and T cell recognition of foreign antigen. While resting T cells bind minimally to beta1 integrin ligands, activation via the CD2 T cell surface receptor results in an increase in functional activity of beta1 integrins without an alteration in beta1 integrin cell surface expression. The objective of this proposal is to identify cytoplasmic regions of the CD2 antigen responsible for upregulation of beta1 integrin activity, with an emphasis on defining the region of the CD2 cytoplasmic domain that mediates an association with phosphatidylinositol 3-kinase (PI 3-K). Antibody stimulation of the CD2 antigen expressed on transfected CD2-negative myelomonocytic HL6O cells results in a rapid up regulation of PI integrin-dependent adhesion to fibronectin. This system will be used to express CD2 molecules with defined mutations in the CD2 cytoplasmic domain. The resulting panel of mutant CD2 transfectants will be analyzed for: 1) ability to bind to fibronectin following CD2 stimulation; 2) association of CD2 with PI 3- K; and 3) PI 3-K enzymatic activity following CD2 stimulation. These HL6O transfectants will also be examined for CD2-dependent changes in PKC activity and actin polymerization. Ultimately, this project will provide new insights into one of the earliest functional responses of T cells to activation, aiding ongoing efforts to exploit adhesion molecules as targets for immunotherapy and cancer treatment.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32AR008438-03
Application #
2700207
Study Section
Special Emphasis Panel (ZRG2-IVP (01))
Project Start
1998-05-01
Project End
Budget Start
1998-05-01
Budget End
1999-03-12
Support Year
3
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Pathology
Type
Schools of Medicine
DUNS #
168559177
City
Minneapolis
State
MN
Country
United States
Zip Code
55455