Molecular Basis of Natural Killer Cell Tumor Target Recognition: the NKr/MHC Class I Complex
Abstract
The original goal was to purify both NK cell receptor molecules (Ly49C) and cognate class I MHC ligands (H2-Kb) to determine the crystal structure of Ly49C bound to Kb. This aim has been achieved by others, using Ly49A and its ligand H2-Dd. The 'missing self' hypothesis is supported by many recent studies. The current goal is to use this knowledge to devise anti-tumor treatments. According to the hypothesis, exposure of NK cell receptors to 'self' class I antigens induces a signal that inactivates the lytic 'positive signal' (by activating phosphatases that dephosphorylate signal molecules). If we treat mice bearing C1498 leukemia cells with non- depleting antibody fragments to NK inhibitory receptors, survival is enhanced. NK cells treated with F(ab')2 blocking antibodies 'purge' leukemic cells from marrow cell suspensions to enhance survival. The aims to pursue preliminary findings are (1) to determine how the tumor cells are killed (apoptosis or necrosis), (2) to develop rapid assays for tumor presence prior to overt disease to improve the ability to evaluate treatment, and (3) extend anti-tumor studies to include use of multiple anti-receptor antibodies, and to use adoptive transfer of activated NK cells 'coated' with blocking antibodies to augment therapy.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2000
- Accession Number
- ADA388883
Entities
People
- Michael Bennett
Organizations
- University of Texas Southwestern Medical Center