Antigenpresenting Cells

Emil R Unanue, Department of Pathology and Center for Immunology, Washington University School of Medicine, St Louis, Missouri, USA

Antigen-presenting cells (APCs) refers to the leukocytes responsible for antigen presentation. These include three sets of cells - the mononuclear phagocytes, the Langerhans-dendritic cells and the B cells.

Other cells can be made to have APC function under special conditions.

Antigen presentation is an obligatory step in the recognition of protein antigens by the T cell lineage.

The APCs bear the molecules encoded in the major histocompatibility complex (MHC), the class I and II molecules. These MHC molecules bind peptides resulting from intracellular processing of the protein. The MHC-peptide complex constitutes the antigenic determinant, the epitope, that engages the T cell receptor. Thus APCs are essential cells for the initiation and maintenance of all T cell responses. (See Antigen Presentation via MHC Class I molecules and Antigen Presentation via MHC Class II molecules.)

APCs need to have several properties in order for them to be involved in presentation to CD4 and CD8 T cells: 1) the capacity to take up the antigen; 2) the capacity to internalize the antigen and process it; 3) the synthesis and expression of MHC class I and II molecules; 4) the expression of adhesion molecules, to promote and insure the APC-T cell interaction; and 5) the expression of costimulator molecules (i.e. those molecules that promote the growth and differentiation of T cells during antigen presentation) and the release of cytokines. The APC-T cell interaction affects both cells; it is symbiotic. The APC changes its biology, becoming activated both in the case of macrophages and B cells; and the T cells respond by entering cell cycle and/or expressing cytokine genes. The activation of T cells is a 'two signal' event, dependent, first, on the engagement of its antigen receptor by peptide-MHC complex (signal 1) and, second, on interactions with the costimulatory mol ecules (signal 2). The major cell interaction molecules are shown in Table 1.

Not all these properties are expressed to the same degree by all the APCs. The differentiation state of APCs, the environment of a given tissue and the nature of the antigen molecule influence APC function. The T cells may also vary in their requirements, depending on their natural history (i.e. unstimulated versus memory cells). Finally, the antigen molecules themselves dictate the extent to which one or another property becomes important, in three ways. First, the physical and chemical form of the antigen determines the extent of uptake by APCs. Whether the antigen is a small molecule or part of a complex structure like that of a bacterium or a virus makes a difference. In the former case the antigen may enter the cell by fluid phase or receptor-mediated endocytosis, while the latter case involves a phagocytic process with internalization of a large extracellular ligand. Along these lines the capacity to internalize a microbe is limited for some APC-like B cells, in contrast to macrophages. Second, the complexity of the antigen will determine the number of peptides derived from its component proteins that become available for binding to MHC proteins. There is no direct estimate of the number of peptides that can be occupied by an MHC molecule when dealing with a bacterium, a complex protein or a simple polypeptide. But the limited studies indicate that the more protein taken up by the APCs, and the more complex the protein.

Table 1 Molecules involved in APC-T cell interaction

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