Info

T Cell Receptor (TCR)

Immunoglobulin (Ig)

Components

a and p chains

Heavy and light chains

Number of Ig domains

One V domain and one C domain in each chain

Heavy chain: one V domain, three or four C domains Light chain: one V domain and one C domain

Number of CDRs

Three in each chain for antigen binding

Three in each chain

Associated signaling molecules

CD3and Z

Iga and Igp

Affinity for antigen (Kd)

10-5-10-7 M

10-7-10-11 M (secreted Ig)

Changes after cellular activation Production of secreted form Isotope switching Somatic mutations

No No No

Yes Yes Yes

FIGURE 7-6 Structure of the T cell receptor. The schematic diagram of the aP TCR (left) shows the domains of a typical TCR specific for a peptide-MHC complex. The antigen-binding portion of the TCR is formed by the Vp and Va domains. The ribbon diagram (right) shows the structure of the extracellular portion of a TCR as revealed by x-ray crystallography. The hypervariable segment loops that form the peptide-MHC binding site are at the top. (Modified from Bjorkman PJ. MHC restriction in three dimensions: a view of T cell receptor/ligand interactions. Cell 89:167-170, 1997. Copyright Cell Press.)

FIGURE 7-6 Structure of the T cell receptor. The schematic diagram of the aP TCR (left) shows the domains of a typical TCR specific for a peptide-MHC complex. The antigen-binding portion of the TCR is formed by the Vp and Va domains. The ribbon diagram (right) shows the structure of the extracellular portion of a TCR as revealed by x-ray crystallography. The hypervariable segment loops that form the peptide-MHC binding site are at the top. (Modified from Bjorkman PJ. MHC restriction in three dimensions: a view of T cell receptor/ligand interactions. Cell 89:167-170, 1997. Copyright Cell Press.)

The Structure of the T Cell Receptor for Antigen

The antigen receptor of MHC-restricted CD4+ helper T cells and CD8+ cytotoxic T lymphocytes (CTLs) is a het-erodimer consisting of two transmembrane polypeptide chains, designated TCR a and p, covalently linked to each other by a disulfide bridge between extracellular cysteine residues (Fig. 7-6). These T cells are called aP T cells. A less common type of TCR, found on y8 T cells, is composed of TCR y and 8 chains. Each TCR a and P chain consists of one Ig-like N-terminal variable (V) domain, one Ig-like constant (C) domain, a hydrophobic transmembrane region, and a short cytoplasmic region. Thus, the extracellular portion of the TCR aP heterodimer is structurally similar to the antigen-binding fragment (Fab) of an Ig molecule, which is made up of the V and C regions of a light chain and the V region and one C region of a heavy chain (see Chapter 5).

The V regions of the TCR a and P chains contain short stretches of amino acids where the variability between different TCRs is concentrated, and these form the hypervariable or complementarity-determining regions (CDRs). Three CDRs in the a chain and three similar regions in the P chain together form the part of the TCR that specifically recognizes peptide-MHC complexes (Fig. 7-7). The P chain V domain contains a fourth hypervariable region that does not appear to participate in antigen recognition but is the binding site for micro-bial products called superantigens (see Chapter 15). Each TCR chain, like Ig heavy and light chains, is encoded by multiple gene segments that undergo somatic rearrangements during the maturation of the T lymphocytes (see Chapter 8).

The C regions of both a and P chains continue into short hinge regions, which contain cysteine residues that contribute to a disulfide bond linking the two chains. The hinge is followed by hydrophobic transmembrane portions, an unusual feature of which is the presence of positively charged amino acid residues, including a lysine residue (in the a chain) or a lysine and an arginine residue (in the P chain). These residues interact with negatively charged residues present in the transmembrane portions of other polypeptides (those of the CD3 complex and Z) that are part of the TCR complex. Both TCR a and P chains have carboxyl-terminal cytoplasmic tails that are 5 to 12 amino acids long. Like membrane Ig on B cells (see later), these cytoplasmic regions are too small to transduce signals, and specific molecules physically associated with the TCR serve the signal-transducing functions of this antigen receptor complex.

The CD3 and Z proteins are noncovalently associated with the TCR ap heterodimer, and when the TCR recognizes antigen, these associated proteins transduce the signals that lead to T cell activation. The components of the TCR complex are illustrated in Figures 7-8 and 7-9. The CD3 proteins and the Z chain are identical in all T cells regardless of specificity, which is consistent with their role in signaling and not in antigen recognition. The CD3 proteins are required not only for signaling in T cells but for surface expression of the functionally complete receptor complex on T cells.

The CD3 y, 8, and e proteins are homologous to each other. The N-terminal extracellular regions of the y, 8, and e chains each contains a single Ig-like domain, and therefore these three proteins are members of the Ig superfamily. The transmembrane segments of all three

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