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CD161 LIGAND, PILAR, FOR

MODULATING ACTIVIATION

AND PROLIFERATION OF T CELLS

 

 

 

 

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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 a pending patent application.  We are seeking an industrial partner interested in its commercialization.

(Ref: J396)

 

 

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