Ia molecules are polymorphic glycoproteins which regulate the major histocompatibility complex (MHC)-restricted recognition of the cooperating cells that bear them with a class of T cells (Class II restricted) that includes the bulk of the T?H? (helper cell) population. On the surface of the antigen-presenting cell (APC), Ia molecules are recognized together with processed exogenous antigen, and thereby trigger the T cell to a differentiative response resulting in """"""""activation,"""""""" i.e., capability to deliver help in an antigen-restricted (Ir-gene controlled) fashion. On the surface of the cell receiving help, Ia molecules promote recognition by the antigen-activated T?H? cell, resulting in delivery of a signal to differentiate. The differential capacities of Ia molecules to promote response to a particular antigenic determinant (Ir gene effect) is dependent on variation in Ia primary structure (amino acid sequence). In addition, there is evidence that secondary structural features (post-translational modifications) of Ia molecules, which vary on functionally different cell types, influence the recognition of Ia by T cells. This work involves: (1) description of secondary structural features of Ia, such as N-linked oligosaccharide, in functionally different cell populations; (2) correlation of such structural features with functions such as antigen-specific T-cell binding and proliferation; and (3) intentional modification of the secondary structure to generate changes in function. We will also be examining the role of a newly discovered chondroitin sulfate proteoglycan (CSPG) specifically associated with Ia in modifying the interaction of Ia with T cells. Methods to be employed are T cell binding and proliferation assays, serial lectin affinity chromatography, exoglycosidase sequencing, and in situ manipulations of la expression or structure by pharmacological, enzymatic, or other approaches. (AG)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA033529-05
Application #
3171370
Study Section
Experimental Immunology Study Section (EI)
Project Start
1982-07-01
Project End
1990-05-31
Budget Start
1986-06-01
Budget End
1987-05-31
Support Year
5
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Washington University
Department
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130