The intrathymic differentiation events leading to the development and export of mature T cells tolerant to self yet capable of responding to foreign peptide antigen in the context of self-MHC are clearly both dynamic and complex. The changing phenotype of the developing thymocyte as
it migrates through and interacts with the heterogeneous thymic microenvironment and the intracellular signalling events associated with such interactions are being extensively studied, yet many aspects remain poorly defined, such as the precise relationship between stromal cells and thymic
selection. Positive and negative selection are crucial events in the development of T cells, leading to a diverse yet non-autoreactive immune system. A breakdown in either of these processes could lead to either a reduced T cell repertoire or the escape into the periphery of autoreactive T
cells – both clearly having deleterious consequences for the health of the individual. This review aims to summarise the current status of research in thymic positive selection with emphasis on the role of different cell types and peptides.