First paragraph of the introduction:
Perhaps one of the greatest attractions of the T lymphocyte to those interested in signal transduction is the diverse roles of the T lymphocyte antigen receptor during development. Early in the life of a T cell, after it has migrated to the thymus, signals initiated by interaction with self-antigen begin a pathway leading to the death and elimination of autoreactive T cells, a process known as negative selection. Also in the thymus, the antigen receptor initiates a signalling pathway that results in the survival of cells having receptors capable of interacting with antigen bound in the antigen-presenting groove of MHC (major histocompatibility complex) molecules expressed on the surface of cells of the host animal -- a process referred to as positive selection. Later in the life of a T cell, after it has migrated to the peripheral lymph nodes, interactions with foreign antigen through the antigen receptor initiate a pathway or differentiation, leading to immunologic activation, proliferation, and differentiation of other cells required for the immune response. How are signals from a single receptor redirected to initiate these different responses? At a descriptive level, present data indicate that the outcome of signalling through the receptor is dictated by the cellular context in which the antigen receptor is activated, often referred to as costimulatory requirements, by the antigen itself, and by developmental windows resulting from cell autonomous processes (Figure 1). Other examples of a receptor determining different cell fates have been described and are instructive by analogy (1). This chapter attempts to place the recent elucidation of steps in the signalling pathway in mature T cells in the context of these more mysterious early developmental events.