In Situ Analysis of T Cell Receptor Signals during Positive Selection

Excerpt

There are many similarities in the T cell receptor (TCR) signaling pathways that support positive selection, deletion of autoreactive T cells in the thymus, and activation of mature T cells in secondary lymphoid organs. However, several unique aspects of this process allow immature T cells endowed with an antigen receptor capable of recognizing foreign peptides in the context of major histocompatibility molecules to survive and differentiate upon low-affinity encounters with self-antigens during development. We review recent advances toward understanding the molecular and cellular mechanisms contributing to the unique TCR signals that support positive selection. In addition, given the dynamism involved in thymocyte scanning of the thymic stroma for appropriate signals, this process has proven difficult to recapitulate in vitro. Accordingly, we discuss the benefits and limitations of current and emerging models of positive selection as well as technologies that are improving our ability to characterize the behavior and TCR signals that accompany positive selection in the complex, three-dimensional environment in which this process occurs.