The antigen-recognition molecules of T cells are made solely as membrane-bound proteins, which are associated with an intracellular signaling complex and function only to signal T cells for activation. These T-cell receptors (TCRs) are related to immunoglobulins both in their protein structure—having both V and C regions—and in the genetic mechanism that produces their great variability, which is discussed in Chapter 5. The T-cell receptor differs from the B-cell receptor in an important way, however: it does not recognize and bind antigen by itself, but instead recognizes short peptide fragments of protein antigens that are presented to them by proteins known as MHC molecules on the surface of host cells.
The MHC molecules are transmembrane glycoproteins encoded in the large cluster of genes known as the major histocompatibility complex (MHC). The most striking structural feature of MHC molecules is a cleft in the extracellular face of the molecule in which peptides can be bound. MHC molecules are highly polymorphic—each type of MHC molecule occurs in many different versions—within the population. These are encoded by slightly different versions of individual genes called alleles. Most people are therefore heterozygous for the MHC molecules: that is, they express two different alleles for each type of MHC molecule, thus increasing the range of pathogen-derived peptides and self-peptides that can be bound. T-cell receptors recognize features of both the peptide antigen and the MHC molecule to which it is bound. This introduces an extra dimension to antigen recognition by T cells, known as MHC restriction because any given T-cell receptor is specific for a particular peptide bound to a particular MHC molecule.
In this chapter we focus on the structure and antigen-binding properties of immunoglobulins and T-cell receptors. Although B cells and T cells recognize foreign molecules in separate distinct fashions, the receptor molecules they use for this task are very similar in structure. We will see how this basic structure can accommodate great variability in antigen specificity, and how it enables immunoglobulins and T-cell receptors to perform their functions as the anti-gen-recognition molecules of the adaptive immune response. With this foundation, we will return to discuss the impact of MHC polymorphism on T-cell antigen recognition and T-cell development in Chapters 6 and 8, respectively.
The structure of a typical antibody molecule.
Antibodies are the secreted form of the B-cell receptor. Because they are soluble and secreted into the blood in large quantities, antibodies are easily obtained and easily studied. For this reason, most of what we know about the B-cell receptor comes from the study of antibodies.
Antibody molecules are roughly Y-shaped, as represented in Fig. 4.1 using three different schematic styles. This part of the chapter will explain how this structure is formed and allows the antibody molecule to perform its dual tasks of binding to a wide variety of antigens while also binding to effector molecules