Some of the B cells and T cells activated by antigen will differentiate into memory cells, the lymphocytes that are responsible for the long-lasting immunity that can follow exposure to disease or vaccination. Memory cells will readily differentiate into effector cells on a second exposure to their specific antigen. Immunological memory is described in Chapter 11.
1-9 Antibodies and T-cell receptors are composed of constant and variable regions that provide distinct functions.
Antibodies were studied by traditional biochemical techniques long before recombinant DNA technology allowed the study of the membrane-bound forms of the antigen receptors on B and T cells. These early studies found that antibody molecules are composed of two distinct regions. One is a constant region, also called the fragment crystallizable region, or Fc region, which takes one of only four or five biochemically distinguishable forms (see Fig. 1.13). The variable region, by contrast, can be composed of a vast number of different amino acid sequences that allow antibodies to recognize an equally vast variety of antigens. It was the uniformity of the Fc region relative to the variable region that allowed its early analysis by X-ray crystallography by Gerald Edelman and Rodney Porter, who shared the 1972 Nobel Prize for their work on the structure of antibodies.
The antibody molecule is composed of two identical heavy chains and two identical light chains. Heavy and light chains each have variable and constant regions. The variable regions of a heavy chain and a light chain combine to form an antigen-binding site that determines the antigen-binding specificity of the antibody. Thus, both heavy and light chains contribute to the antigen-binding specificity of the antibody molecule. Also, each antibody has two identical variable regions, and so has two identical antigen-binding sites. The constant region determines the effector function of the antibody, that is, how the antibody will interact with various immune cells to dispose of antigen once it is bound.
Fig. 1.14 Antigens are the molecules recognized by the immune response, while epitopes are sites within antigens to which antigen receptors bind.
Antigens can be complex macromolecules such as proteins, as shown in yellow. most antigens are larger than the sites on the antibody or antigen receptor to which they bind, and the actual portion of the antigen that is bound is known as the antigenic determinant, or epitope, for that receptor. large antigens such as proteins can contain more than one epitope (indicated in red and blue) and thus may bind different antibodies (shown here in the same color as the epitopes they bind). Antibodies generally recognize epitopes on the surface of the antigen.
Fig. 1.15 T-cell receptors bind a complex of an antigen fragment and a self molecule. unlike most antibodies, t-cell receptors can recognize epitopes that are buried within antigens (first panel). these antigens must first be degraded by proteases (second panel) and the peptide epitope delivered to a self molecule, called an mHC molecule (third panel). It is in this form, as a complex of peptide and mHC molecule, that antigens are recognized by t-cell receptors (tCrs; fourth panel).
The T-cell receptor shows many similarities to the B-cell receptor and antibody (see Fig. 1.13). It is composed of two chains, the TCR αand β chains, that are roughly equal in size and which span the T-cell membrane. Like antibody, each TCR chain has a variable region and a constant region, and the combination of the αand β-chain variable regions creates a single site for binding antigen. The structures of both antibodies and T-cell receptors are described in detail in Chapter 4, and functional properties of antibody constant regions are discussed in Chapters 5 and 10.
1-10 Antibodies and T-cell receptors recognize antigens by fundamentally different mechanisms.