Instead of making α and β chains, a minority of T cells makes a different but related type of TCR heterodimer, composed of γ chains and δ chains. Although these γ/δ T cells normally make up only 5–10% of the T cells in human blood, they can be the dominant T cell population in epithelia (in the skin and gut, for example). They have some properties in common with natural killer (NK) cells and with an enlarging category of T-like cells that have features of both innate and adaptive immune cells, which are sometimes collectively referred to as innate lymphoid cells. The cells in all these categories tend to be enriched in mucosal tissues, respond early to infection, display little immunological memory, and, compared with B and T cells, have surface receptors of restricted diversity. We will not discuss them further.
As with BCRs, TCRs are tightly associated in the plasma membrane with a number of invariant membrane-bound proteins that are involved in passing the signal from an antigen-activated receptor to the cell interior. We will discuss these proteins in more detail later, when we consider some of the molecular events involved in T and B cell activation. First, we consider the special ways in which T cells recognize foreign antigen on the surface of an APC or target cell.
Generally, naïve T cells, including naïve helper and cytotoxic T cells, proliferate and differentiate into effector cells and memory cells only when they see their specific antigen on the surface of an activated dendritic cell in a peripheral lymphoid organ (Figure 24–33). The activated dendritic cell displays the antigen in a complex with MHC proteins on its surface, along with co-stimulatory proteins (see Figure 24–11). The memory T cells that develop, however, can be activated by the same antigen–MHC complex on the surface of other types of APCs (target cells), including macrophages and B cells—as well as by dendritic cells.
Immature dendritic cells are located in most tissues—underlying epithelial layers of the skin and gut, for example—where they are constantly sampling and processing proteins in their environment. They become activated to mature when their pattern recognition receptors (PRRs) encounter pathogen associated molecular patterns (PAMPs) on an invading pathogen or its products. The pathogen or products are ingested, and the microbial proteins are cleaved into peptide fragments, which are loaded onto MHC proteins, as we discuss later. The activated dendritic cells then migrate via the lymph from the site of infection to local lymph nodes or gut-associated lymphoid organs, where they present the foreign antigens, displayed as peptide–MHC complexes on the dendritic cell surface, for recognition by the relevant T cells (see Figure 24–11).
Activated dendritic cells display three types of protein molecules on their surface that have a role in activating a T cell to become an effector cell or memory cell (Figure 24–34): (1) MHC proteins, which present foreign peptides to the TCRs; (2) co‑stimulatory proteins, which bind to complementary receptors on the T cell surface; and (3) cell–cell adhesion molecules, which enable a T cell to bind to the dendritic cell for long enough to become activated, typically several hours. In addition, activated dendritic cells secrete a variety of cytokines that influence the type of effector helper T cell that develops, and different types of dendritic cells promote different outcomes (discussed later).
T cells recognize Foreign peptides Bound to Mhc proteins