T Cell Development Autoimmune disease

Immature thymocytes in the thymus go through selection processes, so called positive and negative selections. Survival of the developing thymocytes is determined by the avidity/affinity of the T cell receptors (TCRs) for peptide/MHC complexes presented by thymic epithelial and dendritic cells.

Only the T cells with TCRs that have low to intermediate avidities to self-peptide/MHC complexes are selected and allowed to mature and migrate to the periphery.

Further development in the periphery of na?ve T cells into fully differentiated T cells equipped with effector functions is also considered to be dependent on TCR recognition of foreign-peptide/MHC complexes. Therefore, the information on the TCRs of T cells reactive to a certain antigen is helpful to dissect how T cell development in the thymus and the periphery is controlled.

With spectratyping/immunoscope analysis, we have established databases of TCR usages involved in a specific minor histocompatibility antigen, which is the basis for making TCR transgenic mice. Together with transgenic mice that express cognate agonist peptides/or altered peptides ubiquitously or in specific tissues, development into specific lineage of effector T cells, and the development and pathogenesis of autoimmune diseases are under investigation.