This is a two-year position is for a post-doctoral scientist with experience in human immunology, cell biology and flow cytometry.
The goal is to determine whether an unique potential for activating T cells is provided by proprietary antibody-based reagents that have been developed by the study sponsor (Elstar Therapeutics) and that engage germline-encoded domains of the V-beta chains of the alpha-beta T cell receptor. This is an extremely important project for several reasons.
- Adrian Hayday’s laboratory has identified a set of butyrophilin-like (BTNL) molecules that critically regulate gamma delta T cell selection and maturation by engaging engage germline-encoded domains of the V-gamma chains of the gamma-delta T cell receptor. Moreover, the laboratory has proposed that the unique biological activities of BTNLs reflects their site-of-engagement on the TCR. If analogous signalling is induced by antibody-based reagents that engage analogous sites on V-beta, the “Hayday hypothesis” would receive strong support, and would argue that T cell receptors should no longer be viewed entirely as clonotypic receptors activated by antigens engaging exclusively unique CDR3 motifs. This would provide a new biological paradigm for human T cell regulation. The proprietary reagents provided by Elstar offer an unique opportunity to investigate this.
- There is intense interest in mechanisms by which T cells can be activated without inducing widespread cytokine release and other aspects of hyperactivation that are commonly associated with the use of the pan T cell activator, anti-CD3. Clearly, V-beta-specific reagents potentially offer a means to activate a defined subset of T cells with immunotherapeutic potential.
- Any identification of an unique signalling induced by engaging V-beta could form the basis of a screen for identifying endogenous, BTNL-like molecules that naturally regulate alpha-beta T cells.
The post holder will be based in the laboratory of Professor Adrian Hayday which has three main locations: the Programme in Infection and Immunity, Floor 2, Borough Wing; CIBCI, New Hunt’s House; and the Francis Crick Institute.
Contact: Adam Laing, Adam.email@example.com