Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

T CELLS AND MHC PROTEINS
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they either kill (if it is an infected host cell, for example) or signal in some way (if
it is a B cell or macrophage, for example). We will refer to such host cells as target
cells. As is the case with APCs, target cells must display an antigen bound to an
MHC protein on their surface for a T cell to recognize them.
There are three main classes of T cells—cytotoxic T cells, helper T cells, and
regulatory T cells. When activated, they function as effector cells (see Figure
24–17), each with their own distinct activities. Effector cytotoxic T cells directly kill
cells that are infected with a virus or some other intracellular pathogen. Effector
helper T cells help stimulate the responses of other immune cells—mainly macrophages,
dendritic cells, B cells, and cytotoxic T cells; as we will see, there are a
variety of functionally distinct subtypes of helper T cells. Effector regulatory T cells
suppress the activity of other immune cells.
In this section, we describe these classes and subclasses of T cells and their
respective functions. We discuss how they recognize foreign antigens on the surface
of APCs or target cells and the crucial part played by MHC proteins in the recognition
process. We begin by considering the cell-surface receptors that T cells
use to recognize antigen.
T Cell Receptors (TCRs) Are Ig‐like Heterodimers
T cell receptors (TCRs), unlike Igs made by B cells, exist only in membrane-bound
form. They are composed of two transmembrane, disulfide-linked polypeptide
chains, each of which contains two Ig‐like domains—one variable and one constant.
On most T cells, the TCRs have one α chain and one β chain (Figure 24–32).
The genetic loci that encode the α and β chains are located on different chromosomes.
Like an Ig heavy-chain locus (see Figure 24–29), the TCR loci contain
separate V, D, and J gene segments (or just V and J gene segments in the case
of the α-chain locus), which are brought together by site-specific recombination
during T cell development in the thymus. With one exception, T cells use the same
mechanisms to generate antigen-binding site diversity of their TCRs as B cells
use to generate antigen-binding site diversity of their Igs, and they use the same
V(D)J recombinase; thus, humans or mice deficient in this recombinase cannot
make functional B or T cells. The mechanism that does not operate in TCR
diversification is antigen-driven somatic hypermutation. Thus, the affinities of
TCRs tend to be low (K a ≈ 10 5 –10 7 liters/mole). Various co-receptors and cell–cell
adhesion proteins, however, greatly strengthen the binding of a T cell to an APC
or target cell.
α chain
V α
C α
(A)
COOH
binding site
H 2N NH 2
S
S
S
S
S S
S
S
S
S
CYTOSOL
β chain
V β
C β
EXTRACELLULAR
SPACE
COOH
plasma
membrane
C α
V α
(B)
S
S
S
S
S
S
S
S
C β
V β
Figure 24–32 A T cell receptor (TCR)
heterodimer. (A) Schematic drawing
showing that the receptor is composed of
an α and a β polypeptide chain. Each chain
has a large extracellular part that is folded
into two Ig‐like domains—one variable
(V) and one constant (C). A V α and a
V β domain (shaded in blue) form the
antigen-binding site. Unlike Igs, which
have two binding sites for antigen, TCRs
have only one. The αβ-heterodimer is
noncovalently associated with a large set
of invariant membrane-bound proteins (not
shown), which help activate the T cell when
the TCRs bind their specific antigen (see
Figure 24–45B). A typical T cell has about
30,000 TCRs on its surface. (B) The threedimensional
structure of the extracellular
part of a TCR. The antigen-binding site
is formed by the hypervariable loops of
both the V α and V β domains (black), and
it is similar in its overall dimensions and
geometry to the antigen-binding site of an
Ig molecule. (B, based on K.C. Garcia et
al., Science 274:209–219, 1996.)