T cells expressing receptors of different affinity for antigen ligands reveal a unique role for p59fyn in T cell development and optimal stimulation of T cells by antigen.

Signaling from the TCR involves the protein tyrosine kinase p59fyn (Fyn). Previous studies have shown that T cell development occurs normally in Fyn-/- mice. In this study, we investigated the requirement for Fyn in the development and function of T cells expressing either the transgenic 2C TCR, with high affinity for its Ag ligand, or the transgenic H-Y TCR, representative of a low affinity TCR. Although Fyn was not essential for positive selection of thymocytes expressing either the 2C or the H-Y TCR, it facilitated the down-regulation of the heat-stable Ag in positively selected CD4-CD8+ thymocytes in both 2C and H-Y mice. Negative selection of thymocytes expressing the H-Y TCR also occurs efficiently in Fyn-/- mice. However, in Fyn-/- mice, there was a preferential survival of thymocytes that expressed higher levels of the CD8 coreceptor and the transgenic TCR. Positively selected CD4-CD8+ thymocytes and peripheral T cells expressing either the 2C or the H-Y TCR differed in their requirement of Fyn for optimal proliferation responses to stimulation by antigenic ligands. Whereas 2C Fyn-/- or 2C Fyn+/+ thymocytes and peripheral T cells responded optimally to stimulation by the specific Ag, H-Y Fyn-/- thymocytes and peripheral T cells were hyporesponsive compared with Fyn+/+ cells. Significantly, in response to a defined low affinity ligand, both 2C Fyn-/- thymocytes and peripheral T cells required Fyn for optimal response to Ag stimulation. Thus, Fyn plays a role during thymocyte development and is required for optimal responses to low affinity/avidity ligands.