T Cell Sensitivity - Isis Project No 1223

Research at the Peter Medawar Building for Pathogen Research has identified mutations in peptide-MHC antigens that improve T cell recognition without altering specificity. These mutant antigens are able to target a specific T cell and deliver an enhanced activation signal. This, in turn can lead to up to a 40 fold increase in effector function (eg. Cytokine production). Such mutant antigens will be of use for boosting immune responses to specific T cell antigens. It has also been shown that T cells respond to lower concentrations of the mutant antigen.

Marketing Opportunity

The mutated antigens, either as soluble molecules or when expressed on the cell surface of an antigen presenting cell, have been shown to enhance T cell signalling and T cell effector function. Importantly, the invention appears to enhance T cell function without altering specificity of the T cell response. As a result, the invention can be used to deliver an enhanced activation signal to a specific T cell of interest without affecting other T cells. This invention has great therapeutic potential as it could be used to specifically enhance an immune response in clinical situations such as viral/bacterial infection and improve the weak CTL response seen in tumour patients. As the mutated antigens are recognised at lower concentration, they may also prove to be of use in diagnostic tests.

In addition, similar but more severe mutations in the MHC have been shown to result in the creation of a peptide-MHC 'superantigen' that can be recognised by all T cells irrespective of the T cell receptor they express. This pMHC class I 'superantigen' does not activate MHC class II-restricted T cells.

The Oxford Invention

The invention comprises a series of mutations in the conserved parts of the MHC class I molecule and can be applied to any such molecule. Surface plasmon resonance has been used to confirm that these mutations do not affect the interaction between the T cell receptor and the peptide-MHC antigen.

Commercial Opportunity

This technology is subject to a patent application. The potential uses of the invention are numerous, and is likely to be applicable to MHC class II-restricted T cells making it an extremely attractive package.

Increased T cell sensitivity and enhanced effector function by peptide-MHC antigen This technology could be applied to any antigen without loss of specificity. The benefits of enhanced effector function and increased ssensitivity are seen when peptide-MHC antigen is presented on the cell surface or as a soluble molecule.

Request Further Information: Project Number 1223 - T Cell Sensitivity