Fig. 4.13 The T-cell receptor resembles a membrane-bound Fab fragment. The fab fragment of an antibody molecule is a disulfide-linked heterodimer, each chain of which contains one immunoglobulin c domain and one V domain; the juxtaposition of the V domains forms the antigen-binding site (see Section 4-6). The T-cell receptor is also a disulfide-linked heterodimer, with each chain containing an immunoglobulin c-like domain and an immunoglobulin V-like domain. As in the fab fragment, the juxtaposition of the V domains forms the site for antigen recognition.
Fig. 4.15 The crystal structure of an α:β T-cell receptor resolved at 0.25 nm. in panels a and b, the α chain is shown in pink and the β chain in blue. Disulfide bonds are shown in green. in panel a, the T-cell receptor is viewed from the side as it would sit on a cell surface, with the cDR loops that form the antigen-binding site (labeled 1, 2, and 3) arrayed across its relatively flat top. in panel b, the cα and cβ domains are shown. The cα domain does not fold into a typical ig-like domain; the face of the domain away from the cβ domain is mainly composed of irregular strands of polypeptide rather than β sheet. The intramolecular disulfide bond (far left) joins a β strand to this segment of α helix. The interaction between the cα and cβ domains is assisted by carbohydrate (colored gray and labeled), with a sugar group from the cα domain making hydrogen bonds to the cβ domain. in panel c, the T-cell receptor is shown aligned with the antigen-binding sites from three different antibodies. This view is looking down into the binding site. The Vα domain of the T-cell receptor is aligned with the VL domains of the antigen-binding sites of the antibodies, and the Vβ domain is aligned with the Vh domains. The cDRs of the T-cell receptor and immunoglobulin molecules are colored, with cDRs 1, 2, and 3 of the TcR shown in red and the hV4 loop in orange. for the immunoglobulin V domains, the cDR1 loops of the heavy chain (h1) and light chain (L1) are shown in light and dark blue, respectively, and the cDR2 loops (h2, L2) in light and dark purple, respectively. The heavy-chain cDR3 loops (h3) are in yellow; the light-chain cDR3s (L3) are in bright green. The hV4 loops of the TcR (orange) have no hypervariable counterparts in immunoglobulins. Model structures courtesy of i.A. Wilson.
There are, however, some distinct structural differences between T-cell receptors and Fab fragments. The most striking is in the Cα domain, where the fold is unlike that of any other Ig-like domain. The half of the Cα domain that is juxtaposed with the Cβ domain forms a β sheet similar to that found in other Ig-like domains, but the other half of the domain is formed of loosely packed strands and a short segment of α helix (see Fig. 4.15b). In a Cα domain the intramolecular disulfide bond, which in Ig-like domains normally joins two β strands, joins a β strand to this segment of α helix.