Antigen presentation is the process of a cell displaying antigen bound by major histocompatibility complex (MHC) proteins on its surface; this is known as antigen presentation. These complexes may be recognised by T cells via their T cell receptors (TCRs). Antigens are processed by APCs and presented to T-cells.
Antigens can be presented in a variety of ways by almost all cell types. They can be found in a wide range of tissues. Professional antigen-presenting cells, such as macrophages, B cells, and dendritic cells, present external antigens to helper T cells, whereas virus-infected cells (or cancer cells) can present cytotoxic T cells with antigens produced inside the cell.
Types and functions
Antigen-presenting cells fall into two categories: professional and non-professional. Those that express MHC class II molecules along with co-stimulatory molecules and pattern recognition receptors are often called professional antigen-presenting cells. The non-professional APCs express MHC class I molecules.
T cells must be activated before they can divide and perform their function. This is achieved by interacting with a professional APC which presents an antigen recognized by their T cell receptor. The APC involved in activating T cells is usually a dendritic cell. T cells cannot recognize (and therefore cannot respond to) “free” or soluble antigens. They can only recognize and respond to antigen that has been processed and presented by cells via carrier molecules like MHC molecules. Helper T cells can recognize exogenous antigen presented on MHC class II; cytotoxic T cells can recognize endogenous antigen presented on MHC class I. Most cells in the body can present antigen to CD8+ cytotoxic T cells via MHC class I; however, the term “antigen-presenting cell” is often used specifically to describe professional APCs. Such cells express MHC class I and MHC class II molecules and can stimulate CD4+ helper T cells as well as cytotoxic T cells.
Professional APCs specialize in presenting antigens to T cells. They are very efficient at internalizing antigens, either by phagocytosis (e.g. macrophages), or by receptor-mediated endocytosis (B cells), processing the antigen into peptide fragments and then displaying those peptides (bound to a class II MHC molecule) on their membrane. The T cell recognizes and interacts with the antigen-class II MHC molecule complex on the membrane of the antigen-presenting cell. An additional co-stimulatory signal is then produced by the antigen-presenting cell, leading to activation of the T cell. The expression of co-stimulatory molecules and MHC class II are defining features of professional APCs. All professional APCs also express MHC class I molecules as well.
The main types of professional antigen-presenting cells are dendritic cells, macrophages and B cells.
Dendritic cells (DCs)
Dendritic cells have the broadest range of antigen presentation and are necessary for activation of naive T cells. DCs present antigen to both helper and cytotoxic T cells. They can also perform cross-presentation, a process by which they present exogenous antigen on MHC class I molecules to cytotoxic T cells. Cross-presentation allows for the activation of these T cells. Dendritic cells also play a role in peripheral tolerance, which contributes to prevention of auto-immune disease.
Prior to encountering foreign antigen, dendritic cells express very low levels of MHC class II and co-stimulatory molecules on their cell surface. These immature dendritic cells are ineffective at presenting antigen to T helper cells. Once a dendritic cell’s pattern-recognition receptors recognize a pathogen-associated molecular pattern, antigen is phagocytosed and the dendritic cell becomes activated, upregulating the expression of MHC class II molecules. It also upregulates several co-stimulatory molecules required for T cell activation, including CD40 and B7. The latter can interact with CD28 on the surface of a CD4+ T cell. The dendritic cell is then a fully mature professional APC. It moves from the tissue to lymph nodes, where it encounters and activates T cells.