Читать книгу Immunology - Richard Coico - Страница 117

There is a large body of evidence indicating that the properties of many epitopes recognized by B cells differ from those recognized by T cells (Table 5.1). In general, membrane‐bound antibody present on B cells recognizes and binds free antigen in solution. Thus, these epitopes are typically on the outside of the molecule, accessible for interaction with the B‐cell receptor. Terminal side chains of polysaccharides and hydrophilic portions on protein molecules generally constitute B‐cell epitopes. An example of an antigen with five linear B‐cell epitopes located on the exposed surface of myoglobulin is shown in Figure 5.3. B‐cell epitopes may also form as a result of the folded conformation of molecules as shown in Figure 5.4. Such epitopes are called conformational or discontinuous epitopes, where noncontiguous residues along a polypeptide chain are brought together by the folded conformation of the protein, as shown in Figure 5.3. In contrast to B cells, T cells are unable to bind soluble antigen. The interaction of an epitope with the TCR requires APC processing of the antigen in which enzymatic degradation takes place to yield small peptides, which then associate with the MHC. Thus, T‐cell epitopes can only be continuous or linear because they are composed of a single segment of a polypeptide chain.

Figure 5.3. Example of antigen (sperm whale myoglobin) containing five linear B‐cell epitopes (red), one of which is bound to the antibody‐binding site of antibody specific for amino acid residues 56–62.

Figure 5.5 illustrates the structural organization of a class I MHC with an antigenic peptide bound to it. Generally, such processed epitopes are internal denatured linear hydrophobic areas of proteins. Polysaccharides do not yield such areas and indeed are not known to bind or activate T cells. Thus, polysaccharides contain solely B‐cell recognizable epitopes, whereas proteins contain both B‐ and T‐cell recognizable epitopes (see Table 5.1). Antigenic epitopes may have the characteristics shown schematically in Figure 5.6. Thus, they may consist of a single epitope (hapten) or have varying numbers of the same epitope on the same molecule (e.g., polysaccharides). The most common antigens (proteins) have varying numbers of different epitopes on the same molecule.

TABLE 5.1. Antigen Recognition by B and T Cells

Characteristic	B cells	T cells
Antigen interaction	B‐cell receptor (BCR) binds antigen (Ag)	T‐cell receptor (TCR) binds antigenic peptides bound to MHC
Nature of antigens	Protein, polysaccharide, lipid	Peptide
Binding soluble antigens	Yes	No
Epitopes recognized	Accessible, sequential, or nonsequential	Internal linear peptides produced by antigen processing (proteolytic degradation)

Figure 5.4. Antigen showing amino acid residues (circles), which form a nonsequential epitope “loop” (blue) resulting from the disulfide bond between residues 64 and 80. Note the binding of an epitope‐specific antibody to the nonsequential amino acids that constitute the epitope.

Figure 5.5. Structure of a MHC class I molecule (ribbon diagram) with antigenic peptide (ball‐and‐stick model).