T lymphocyte–mediated cellular immunity is responsible for protection against intracellular pathogens. T cells also mediate pathological responses in autoimmune diseases, chronic inflammatory conditions, and allograft rejection. These protective and pathological roles for T cells require the recognition of antigens on the surface of other cells. This chapter reviews how endothelial cells (ECs) may play a unique role in regulating T cell–mediated immune responses by presenting antigen to circulating T cells within the lumens of blood vessels. Antigen presentation to T cells may be considered a complex output function of ECs, which is dependent on the regulated expression of several intracellular and cell surface proteins. ECs may also become susceptible to both physiological and pathological input signals as a consequence of their intimate relationships with T lymphocytes. In this chapter, a brief overview of the cell biology of antigen presentation to T cells is followed by a discussion of specific features of antigen presentation by ECs.

BACKGROUND: ANTIGEN PRESENTATION AND T-CELL HOMING

T cells are heterogeneous with respect to effector functions and history of antigen exposure. This heterogeneity is reflected in their differing requirements for activation. Regardless of the subset, T cells must recognize antigen via cell surface antigen receptors – called T-cell receptors (TCRs) – for functional activation to proceed. Most T lymphocytes recognize a complex of a proteolytically derived peptide bound to one of many possible allelic forms of a major histocompatibility complex (MHC) molecule that is expressed on the surface of another cell. These peptide–MHC complexes are the “antigens” to which the TCR binds.