Figure 1.

T-cell activation is regulated by antigen presentation, as well as stimulatory and inhibitory co-receptors. (A) Overview of the MHC I and II antigen presentation and processing pathways. Canonical pathways of MHC I antigen presentation allow display of intracellular proteins following processing and transport to circulating CD8⁺ T lymphocytes. Canonical MHC II antigen presentation allows display of antigens derived from the extracellular environment to circulating CD4⁺ T lymphocytes. (B) Signals required for proper T-cell activation. Both CD4⁺ and CD8⁺ T cells are activated following interaction with signal 1 provided through presentation of MHC I or II/peptide complexes at the cell surface with the T-cell receptor (TCR), as well as signal 2 supplied by interaction of CD80/CD86 costimulation molecules expressed on antigen-presenting cells (APCs) with CD28 expressed on T cells. Only in presence of both signals will naive T cells be activated. Following activation, T cells may recognize and kill cells presenting only signal 1 (MHC/peptide). (C) Signaling pathways engaged following interaction of T cells with signals 1 and 2. T cells stimulated through the TCR engage MAPK pathway signaling, which results in production of cytokines such as IL-2. Signal 2 targets PI3K/AKT signaling, through which T-cell survival and proliferation result. Both signals are crucial for initial T-cell activation. (D) Overview of the receptors and ligands expressed on T cells and APCs, which may influence T-cell activation upon interaction. Several of these receptors may be expressed on T cells following T-cell activation as a mechanism to inhibit T-cell activation and prevent autoimmune disease.