Summary to Chapter 4.
B cells and T cells use different, but structurally similar, molecules to recognize antigen. The antigen-recognition molecules of B cells are immunoglobulins, and are made both as a membrane-bound receptor for antigen, the B-cell receptor, and as secreted antibodies that bind antigens and elicit humoral effector functions. The antigen-recognition molecules of T cells, in contrast, are made only as cell-surface receptors and so elicit only cellular effector functions. Immunoglobulins and T-cell receptors are highly variable molecules, with the variability concentrated in that part of the molecule—the variable (V) region—that binds to antigen. Immunoglobulins bind a wide variety of chemically different antigens, whereas the major type of T-cell receptor, the α:β T-cell receptor, predominantly recognizes peptide fragments of foreign proteins bound to MHC molecules, which are ubiquitous on cell surfaces.
Binding of antigen by immunoglobulins has chiefly been studied with antibodies. The binding of antibody to its antigen is highly specific, and is determined by the shape and physicochemical properties of the antigen-binding site. Located at the other end of the antibody from the antigen-binding site is the constant, or Fc, region, which influences the types of effector function the antibody can elicit. There are five main functional classes of antibodies, each encoded by a different type of constant region. As we will see in Chapter 10, these interact with different components of the immune system to incite an inflammatory response and eliminate the antigen.
T-cell receptors differ in several respects from the B-cell immunoglobulins. One is the absence of a secreted form of T-cell receptor, reflecting the functional differences between T cells and B cells. B cells deal with pathogens and their protein products circulating within the body; secretion of a soluble antigen-recognition molecule enables the B cell to act in the clearance of antigen effectively throughout the extracellular spaces of the body. T cells, in contrast, are specialized for active surveillance of pathogens, and T-cell recognition does not involve a soluble, secreted receptor. Some, such as CD8 T cells, are able to detect intracellular infections and are able to kill infected cells that bear foreign antigenic peptides on their surface. Others, such as CD4 T cells, interact with cells of the immune system that have taken up foreign antigen and are displaying it on the cell surface.
T-cell receptors also recognize a composite ligand made up of the foreign peptide bound to a self MHC molecule, and not intact antigen. This means that T cells can interact only with a body cell displaying the antigen, not with the intact pathogen or protein. Each T-cell receptor is specific for a particular combination of peptide and a self MHC molecule. MHC molecules are encoded by a family of highly polymorphic genes. Expression of multiple variant MHC molecules, each with a different peptide-binding repertoire, helps to ensure that T cells from an individual will be able to recognize at least some peptides generated from nearly every pathogen.
Questions.
4.1 True or False: An antibody proteolytically cleaved by papain yields a fragment with higher avidity to the cognate antigen than an antibody cleaved by pepsin.
4.2 Short Answer: how is cD4 and cD8 co-receptor binding to Mhc important for T-cell receptor signaling?
4.3 Short Answer: Why and how is it advantageous to have heterozygosity in the Mhc locus?
4.4 Matching: Match the term to the best description:
A. Antigenic determinant i. The structure recognized by an antibody (that is, the epitope)
B. conformational/ ii. Regions of the V region
C. continuous/linear iii. An epitope composed epitope of a single segment of a polypeptide chain