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CD161 Ligand, PILAR, for Modulating Activation and Proliferation of T Cells

CD161 is a C-type lectin receptor initially associated with murine NK cells. Unlike murine lymphocytes, the expression of CD161 in human T cells identifies mostly memory lymphocytes and only a small proportion of invariant NK T cells. CD161 engagement in humans has been recently associated with the enhancement of IFN-γ and TNF-α production in the context of a T cell receptor (TCR) signal, while inducing the production of IL-12 by dendritic cells. The only previously identified ligand of CD161 is CLEC2D/LLT1, another C-type lectin molecule mapping in the vicinity of NKG2D at the NK cluster.

Dartmouth researchers have now identified a new ligand for CD161 that acts as a co-stimulatory signal through T:T cell interactions. This protein, designated Proliferation-Induced Lymphocyte-Associated Receptor (PILAR) is detected on a fraction of T cells infiltrating synovial fluid specimens from gout and rheumatoid arthritis patients using monoclonal antibodies newly generated by the researchers. PILAR is over-expressed upon early T cell activation and enhances TCR-dependent stimulation through CD161 by up-regulating anti-apoptotic genes. In contrast, PILAR induces apoptotic T cell death through a second receptor if CD161 is blocked. This crucial role for PILAR in modulating the extent of cellular adaptive immune responses in humans provides a basis for using PILAR, as well as PILAR agonists and antagonists, for modulating immune responses in the treatment of cancer, autoimmune diseases or inflammation.

This technology is claimed in the published PCT Application No. PCT/US2008/059879. We are seeking an industrial partner interested in its commercialization. (Ref: J396)

Last Updated: 7/24/12