The recognition of proteins and peptides by antibodies.

Abstract

Immunological recognition is mediated by T and B lymphocytes and by immunoglobulin molecules secreted by plasmocytes. The T cells recognize protein antigens by means of their T-cell receptors (TCRs) after the antigen has been processed into peptide fragments, a topic discussed in Chapter 13. The B cells recognize antigens by means of B-cell immunoglobulin receptors, which are actually antibody molecules anchored in the B-cell membrane. Unlike T-cell receptors, B-cell receptors are able to recognize the native tertiary structure of a protein antigen. The antibody molecules that are subsequently released by the B cell, after its differentiation into a plasmocyte. possess the same specificity as the receptors of the triggered B cell; therefore, they are also able to recognize the native conformation of the protein antigen. The first selective theory of antibody diversity was developed at the beginning of the century by Paul Ehrlich, who proposed his “side chain” theory to explain the appearance of specific antibodies. According to this theory, lymphocytes possess on their surface a variety of side chain groups or receptors that are able to combine in a specific manner with different antigens. The interaction of the antigen with one of the side chains was believed to result in the release of that side chain group from the cell surface and to trigger the subsequent synthesis and release of large numbers of the same side chains. According to Ehrlich, the antigen selects, on the surface of the lymphocyte, a receptor with a complementary shape, and it induces the cells to excrete large numbers of this receptor in the form of specific antibodies. This side chain theory is remarkably modern, since it is similar to the currently accepted clonal selection mechanism, which links the specificity of antibodies appearing in the serum with the presence of preexisting clones of cells possessing the same antibodies immobilized at the cell surface. The molecular mechanisms of antigen recognition by an antibody anchored in the B-cell membrane or by a free antibody molecule are the same. However, it is much easier to study the binding of antigens to free antibodies than to antibodies attached to B cells, and most of our knowledge concerning antigen-antibody binding has been derived from studies with free antibody molecules. The term antigen refers to any entity that is able to generate an immune response in higher vertebrates and to be recognized by the products of the immune response. The ability of antigens to react specifically with complementary antibodies is known as antigenic reactivity, and their