The proposed studies will attempt to define the function of a family of lectin-like proteins, designated NKG2, that is expressed primarily on NK cells. All studies will be carried out on two family members, NKG2-A and NKG2-D, that have very different amino acid sequences throughout their lectin domains and, thus, probably have different ligand specificities. cDNA fragments encoding these two proteins will be introduced into a number of procaryotic and eucaryotic expression vectors to create reagents and cell lines for subsequent studies. Polyclonal and monoclonal antibodies will be generated against these expression products. A number of assays are planned to test for the ability of the NKG2 proteins, when bound either by the natural ligand or by anti-NKG2 monoclonal antibodies, to trigger a cytolytic response or deliver a transmembrane signal. These assays will be carried out on an NK cell population and on NKG2-transfected T cell lines. Eucaryotic expression products will also be used to identify cells that express the NKG2 target ligands.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Modified Research Career Development Award (K04)
Project #
5K04CA001665-03
Application #
2084238
Study Section
Experimental Immunology Study Section (EI)
Project Start
1992-08-15
Project End
1997-07-31
Budget Start
1994-08-01
Budget End
1995-07-31
Support Year
3
Fiscal Year
1994
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
Houchins, J P; Lanier, L L; Niemi, E C et al. (1997) Natural killer cell cytolytic activity is inhibited by NKG2-A and activated by NKG2-C. J Immunol 158:3603-9
Adamkiewicz, T V; McSherry, C; Bach, F H et al. (1994) Natural killer lectin-like receptors have divergent carboxy-termini, distinct from C-type lectins. Immunogenetics 39:218
Chambers, W H; Adamkiewicz, T; Houchins, J P (1993) Type II integral membrane proteins with characteristics of C-type animal lectins expressed by natural killer (NK) cells. Glycobiology 3:9-14