Professor Julian Dyson

T Cell Development

T cell selection in the thymus produces peripheral repertoires containing both effector and regulatory T cells. This process is dependent on the interaction between the T cell receptor on developing thymocytes and self-MHC-peptide. The highly polymorphic MHC class I and II molecules also encode the strongest genetic association with predisposition to autoimmunity. 

To investigate this association, we are exploring the molecular basis for recognition of MHC by the T cell receptor and the roles of the complementarity determining regions. A defective regulatory T cell compartment has been implicated in the breakdown of self-tolerance in autoimmunity. We have been analysing regulatory T cell development in the NOD model of type I diabetes and find TCR diversity within the thymic regulatory T cell compartment is limited in comparison with non-autoimmune mice. The basis for altered regulatory T cell development in NOD is currently being investigated. A fuller understanding of these fundamental aspects of T cell immunity will provide new insight into the aetiology of human autoimmune disease.

Current research publications:

Furmanski, A. L., Bartok, I, Chai, J.-G., Singh, Y., Ferreira, C., Scott, D., Holland, S. J., Bourdeaux, C., Crompton, T. and Dyson, J. Peptide specific, TCR-alpha driven, co-receptor independent negative selection in TCR a-chain transgenic mice. J. Immunology (2010) 184:650-57. Publisher weblink

Ferreira, C., Singh, Y., Furmanski, A. L., Wong, F. S., Garden, O. A. and Dyson J. Non-obese diabetic mice select a low-diversity repertoire of natural regulatory T cells. Proc. Natl. Acad. Sci. U S A. (2009) 106:8320-5. Publisher weblink

Pennington, D., Silva-Santos, B., Silberzahn, T., Escorcio-Correia, M., Woodward, M., Roberts, S., Smith, A., Dyson, J. and Hayday, A. Early events in the thymus affect the balance of effector and regulatory T cells. Nature (2006) 444: 1073-77. Publisher weblink