Antigen Capture And The Functions Of Antigenpresenting Cells

The realization that various cells other than T cells are needed to present antigens to T lymphocytes came first from studies in which protein antigens that were known to elicit T cell responses were labeled and injected into mice, to ask what cells bound (and, by implication, recognized) these antigens. The surprising result was that the injected antigens were associated mainly with non-T cells. This type of experiment was quickly followed by studies showing that protein antigens that were physically associated with macrophages were much more immunogenic, on a molar basis, than the same antigens injected into mice in soluble form. In these early experiments, the macrophage populations studied likely included dendritic cells, since, as discussed below, naive T cells are best activated by dendritic cells. Subsequent cell culture experiments showed that purified CD4+ T cells could not respond to protein antigens, but they responded very well if non-T cells such as dendritic cells or macrophages were added to the cultures. These results led to the concept that a critical step in the induction of a T cell response is the presentation of the antigen to T lymphocytes by other cells, and the name antigen-

presenting cells was born. The first APCs identified were macrophages, and the responding T cells were CD4+ helper cells. It soon became clear that several cell populations, described later, can function as APCs in different situations. By convention, APC is still the term used to refer to specialized cells that display antigens to CD4+ T lymphocytes; as we shall see later in the chapter, all nucleated cells can display protein antigens to CD8+ T lymphocytes, and they are not called APCs.

We begin with a discussion of some of the general properties of APCs for CD4+ T lymphocytes.

• Different cell types function as APCs to activate naive and previously differentiated effector T cells (Fig. 6-2 and Table 6-2). Dendritic cells are the most effective APCs for activating naive T cells and therefore for initiating T cell responses. Macrophages and B lymphocytes also function as APCs, but mostly for previously activated CD4+ helper T cells rather than for naive T cells. Their roles as APCs are described later in this chapter and in more detail in Chapters 10 and 11. Dendritic cells, macrophages, and B lymphocytes express class II MHC molecules and other molecules involved in stimulating T cells and are therefore capable of activating CD4+ T lymphocytes. For this reason, these three cell types have been called professional APCs; however, this term is sometimes used to refer only to dendritic cells because this is the only cell type whose dedicated function is to capture and present antigens and the only APC capable of initiating primary T cell responses.

Antigen uptake

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