8536ach03057-0758/7/029:18 AM Page63mac79Mac79:45Bw: Goosby et Immunology 5e: Antigens CHAPTER 3 TABLE 3-4 Comparison of antigen recognition by T cells and B cells Characteristic B cells T cells Interaction with antigen Involves binary complex of membrane Involves ternary complex of T-cell receptor, Ag, lg and Ag and MHC molecule Binding of soluble antigen Involvement of mhc molecules Required to display processed antigen de, lipid les Accessible, hydrophilic, mobile peptide Internal linear peptides produced by containing sequential or nonsequential processing of antigen and bound to amino acids MHC molecules the sequences of amino acids in the binding site and the that make up the binding site. Despite differences in the chemical environment that they produce. binding patterns of small haptens and large antigens, Chap Smaller ligands such as carbohydrates, small oligonu- ter 4 will show that all antibody binding sites are assembled cleotides, peptides, and haptens often bind within a deep from the same regions of the antibody molecule--namely, pocket of an antibody. For example, angiotensin Il, a small parts of the variable regions of its polypeptide chains octapeptide hormone, binds within a deep and narrow horne(725 A2)of a monoclonal antibody specific for the hormone(Figure 3-2). Within this groove, the bound pep- tide hormone folds into a compact structure with two turns, which brings its amino(N-terminal) and carboxyl(C-termi nal)termini close together. All eight amino acid residues of the octapeptide are in van der Waals contact with 14 residues of the antibodys groove. a quite different picture of epitope structure emerges from x-ray crystallographic analyses of monoclonal antibod ies bound to globular protein antigens such as hen egg-white lysozyme(HEL)and neuraminidase(an envelope glycopro tein of influenza virus). These antibodies make contact with the antigen across a large flat face(Figure 3-3). The interact- ing face between antibody and epitope is a flat or undulating surface in which protrusions on the epitope or antibody are matched by corresponding depressions on the antibody or epitope. These studies have revealed that 15-22 amino acids on the surface of the antigen make contact with a similar number of residues in the antibodys binding site; the surface area of this large complementary interface is between 650 A and 900 A2. For these globular protein antigens, then,the shape of the epitope is entirely determined by the tertiary conformation of the native protein. Thus, globular protein antigens and small peptide anti- gens interact with antibody in different ways( Figure 3-4). Typically, larger areas of protein antigens are engaged by the antibody binding site. In contrast, a small peptide such as an- giotensin II can fold into a compact structure that occupies less space and fits into a pocket or cleft of the binding site. This pattern is not unique to small peptides; it extends to the FIGURE 3.2 Three-dimensional structure of an octapeptide hor binding of low-molecular-weight antigens of various chemi- mone(angiotensin Il)complexed with a monoclonal antibody Fab I types. However, these differences between the binding of fragment, the antigen-binding unit of the antibody molecule. The an- small and large antigenic determinants do not reflect funda- giotensin ll peptide is shown in red, the heavy chain in blue, and the mental differences in the regions of the antibody molecule light chain in purple. From K C Garcia et al., 1992, Science 257: 502.1the sequences of amino acids in the binding site and the chemical environment that they produce. Smaller ligands such as carbohydrates, small oligonu￾cleotides, peptides, and haptens often bind within a deep pocket of an antibody. For example, angiotensin II, a small octapeptide hormone, binds within a deep and narrow groove (725 Å2 ) of a monoclonal antibody specific for the hormone (Figure 3-2). Within this groove, the bound pep￾tide hormone folds into a compact structure with two turns, which brings its amino (N-terminal) and carboxyl (C-termi￾nal) termini close together. All eight amino acid residues of the octapeptide are in van der Waals contact with 14 residues of the antibody’s groove. A quite different picture of epitope structure emerges from x-ray crystallographic analyses of monoclonal antibod￾ies bound to globular protein antigens such as hen egg-white lysozyme (HEL) and neuraminidase (an envelope glycopro￾tein of influenza virus). These antibodies make contact with the antigen across a large flat face (Figure 3-3). The interact￾ing face between antibody and epitope is a flat or undulating surface in which protrusions on the epitope or antibody are matched by corresponding depressions on the antibody or epitope. These studies have revealed that 15–22 amino acids on the surface of the antigen make contact with a similar number of residues in the antibody’s binding site; the surface area of this large complementary interface is between 650 Å2 and 900 Å2 . For these globular protein antigens, then, the shape of the epitope is entirely determined by the tertiary conformation of the native protein. Thus, globular protein antigens and small peptide anti￾gens interact with antibody in different ways (Figure 3-4). Typically, larger areas of protein antigens are engaged by the antibody binding site. In contrast, a small peptide such as an￾giotensin II can fold into a compact structure that occupies less space and fits into a pocket or cleft of the binding site. This pattern is not unique to small peptides; it extends to the binding of low-molecular-weight antigens of various chemi￾cal types. However, these differences between the binding of small and large antigenic determinants do not reflect funda￾mental differences in the regions of the antibody molecule that make up the binding site. Despite differences in the binding patterns of small haptens and large antigens, Chap￾ter 4 will show that all antibody binding sites are assembled from the same regions of the antibody molecule—namely, parts of the variable regions of its polypeptide chains. Antigens CHAPTER 3 63 TABLE 3-4 Comparison of antigen recognition by T cells and B cells Characteristic B cells T cells Interaction with antigen Involves binary complex of membrane Involves ternary complex of T-cell receptor, Ag, Ig and Ag and MHC molecule Binding of soluble antigen Yes No Involvement of MHC molecules None required Required to display processed antigen Chemical nature of antigens Protein, polysaccharide, lipid Mostly proteins, but some lipids and glycolipids presented on MHC-like molecules Epitope properties Accessible, hydrophilic, mobile peptides Internal linear peptides produced by containing sequential or nonsequential processing of antigen and bound to amino acids MHC molecules FIGURE 3-2 Three-dimensional structure of an octapeptide hor￾mone (angiotensin II) complexed with a monoclonal antibody Fab fragment, the antigen-binding unit of the antibody molecule. The an￾giotensin II peptide is shown in red, the heavy chain in blue, and the light chain in purple. [From K. C. Garcia et al., 1992, Science 257:502.] 8536d_ch03_057-075 8/7/02 9:18 AM Page 63 mac79 Mac 79:45_BW:Goldsby et al. / Immunology 5e: