Fig. 7.8 The T-cell receptor complex is made up of variable antigen-recognition proteins and invariant signaling proteins. upper panel: the functional T-cell receptor (TcR) complex is composed of the antigen-binding TcRα:β heterodimer associated with six signaling chains: two ε, one δ, and one γ collectively called cd3, and a homodimer of ζ. cell-surface expression of the antigen-binding chains requires assembly of TcRα:β with the signaling subunits. each cd3 chain has one immunoreceptor tyrosine-based activation motif (iTam), shown as a yellow segment, whereas each ζ chain has three. The transmembrane regions of each chain have unusual acidic or basic residues as shown. Lower panel: the transmembrane regions of the various TcR subunits are represented in cross-section. it is thought that one of the positive charges, from a lysine (K) of the α chain, interacts with the two negative charges of aspartic acid (d) of the cd3δ:ε dimer, while the other positive charge, of arginine (R), interacts with aspartic acids of the ζ homodimer. The positive arginine (K) charge of the β chain interacts with the negative charges of aspartic acid and glutamic acid (e) in the cd3γ:ε dimer.
in the B-cell receptor, and the TCRα and TCRβ chains in the T-cell receptor. These variable chains have exquisite specificity for antigen, allowing each lymphocyte to detect the presence of one type of pathogen. However, binding of antigen to the antigen receptor is not sufficient for a lymphocyte to respond— the information that antigen receptor engagement has occurred also needs to be transduced into the intracellular compartment of the lymphocyte. Thus, the fully functional antigen receptor complex must include proteins that can transduce a signal across the plasma membrane. For the B-cell antigen receptor and the T-cell antigen receptor, this function is mediated by invariant accessory proteins that initiate signaling when the receptors bind antigen. Assembly with these accessory proteins is also essential for transport of the receptor to the cell surface. In this part of the chapter we describe the structure of the antigen receptor complexes on T cells and B cells, and the signaling pathways that lead from them.
7-7 Antigen receptors consist of variable antigen-binding chains associated with invariant chains that carry out the signaling function of the receptor.
In T cells, the highly variable TCRα:β heterodimer (see Chapter 5) is not sufficient on its own to make up a complete cell-surface antigen receptor. When cells were transfected with cDNAs encoding the TCRα and TCRβ chains, the heterodimers formed were degraded and did not appear on the cell surface. This implied that other molecules are required for the T-cell receptor to be expressed on the cell surface. In the T-cell receptor, the other required molecules are the CD3γ, CD3δ, and CD3ε chains, which together form the CD3 complex; and the ζ chain, which is present as a disulfide-linked homodimer (Fig. 7.8). The CD3 proteins have an extracellular immunoglobulin-like domain, whereas the ζ chain contains only a short extracellular domain. Throughout the remainder of the chapter, we will use the term T-cell receptor to refer to the entire T-cell receptor complex, including these associated signaling subunits.