Mak Lab

Molecular Immunology

Role of Nkrp1 in Immune Responses

The goal of my research work is to evaluate the contribution of non-MHC receptors in natural killer (NK) cell development and function, and immunity to cancer and virus infections.

NKR-P1 receptors are homodimeric type II transmembrane C-type lectin-like molecules expressed on NK cells. This receptor family consists of five members in mice (NKR-P1A, NKR-P1B/D, NKR-P1C, NKR-P1F and NKR-P1G; Nkrp1e is a pseudogene), which include both inhibitory and activating receptors. Ligands for most NKR-P1 receptors have been identified as members of the C-type lectin-related family (Clr) of membrane glycoproteins encoded by the Clec2 genes, which are intermingled among the Nkrp1 (Klrb1) genes within the mouse NK gene complex (NKC) on mouse chromosome 6. The currently known receptor-ligand pairs for this family include: NKR-P1B:Clr-b, NKR-P1F:Clr-c,d,g and NKR-P1G:Clr-d,f,g. The NKR-P1B:Clr-b receptor:ligand pair resemble the Ly49:MHC-I recognition system in many ways. Like the majority of Ly49 receptors, NKR-P1B is an inhibitory receptor which is expressed on a subset of NK cells. Its ligand, Clr-b, like MHC-I, is broadly expressed on hematopoietic cells. This is in contrast to other Clr family members, whose expression appears to be more tissue-restricted. In further similarity to MHC-I, Clr-b expression on transfected cells confers resistance to lysis by NK cells. Therefore, the NKR-P1B:Clr-b interactions represent an MHC-I-independent missing-self recognition system to monitor cellular levels of Clr-b.

We have generated an NKR-P1B-deficient mouse strain to study the following:

1. Role of NKR-P1B:Clr-b interactions in NK cell development and function.
2. Role of NKR-P1B receptor in cancer immune surveillance by NK cells.
3. Role of NKR-P1B receptor in immunity against virus infections.