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Mouse NKR-P1B, a novel NK1.1 antigen with inhibitory function.
J R Carlyle1, A Martin, A Mehra
1Departments ofImmunology and Anatomy and Cell Biology, University of Toronto, Toronto, Ontario, Canada.
Journal of Immunology (Baltimore, Md. : 1950)
|May 7, 1999
Summary
Mouse NK1.1 antigen (Ag) has two forms: NKR-P1C activates NK cells, while NKR-P1B inhibits them. This discovery reveals dual roles for NKR-P1 molecules in regulating NK cell function.
Area of Science:
- Immunology
- Cellular Biology
- Molecular Biology
Background:
- The mouse NK1.1 antigen (Ag) was initially identified as NK cell receptor (NKR)-P1C, a molecule mediating NK cell activation.
- The CD161 family in mice comprises several members involved in NK cell regulation.
Purpose of the Study:
- To identify and characterize novel NK1.1 Ags within the mouse CD161 family.
- To elucidate the functional roles of different NK1.1 Ags in NK cell activation and inhibition.
Main Methods:
- Utilized immunological assays to define NK1.1 Ags.
- Investigated the association of NKR-P1B with intracellular signaling molecules.
- Analyzed the impact of NKR-P1B on NK cell activation.
Main Results:
- Identified NKR-P1B as a novel NK1.1 Ag.
- Demonstrated that NKR-P1B inhibits NK cell activation, contrasting with the activating function of NKR-P1C.
- Showed that NKR-P1B associates with Src homology 2-containing protein tyrosine phosphatase-1, providing a mechanism for inhibition.
Conclusions:
- The mouse CD161 family contains NK1.1 Ags with opposing functions (activation vs. inhibition).
- NKR-P1B functions as an inhibitory NK receptor, mediated by its association with SHP-1.
- These findings suggest NKR-P1 molecules play a critical role in regulating NK cell activity, similar to the Ly-49 family.
