Rucete ✏ Lehninger Principles of Biochemistry In a Nutshell
5.2 Complementary Interactions between Proteins and Ligands: The Immune System and Immunoglobulins
This chapter introduces the principles of specific and reversible binding between proteins and ligands in the context of the immune system, focusing on how antibodies (immunoglobulins) bind antigens, the structure and diversity of immunoglobulins, and their roles in physiology and analytical applications.
The Immune System and Protein-Ligand Recognition
• Most protein-ligand interactions occur at clefts or surfaces lined with specific amino acid residues, allowing for highly specific and discriminatory binding—even among similar ligands.
• The adaptive immune system of vertebrates, evolved around 500 million years ago, relies on a vast diversity of protein variants (receptors and antibodies) that distinguish self from nonself and defend against pathogens.
• Immune responses are coordinated by various leukocytes (white blood cells) like macrophages and lymphocytes, which arise from stem cells and produce proteins that recognize infection signals.
• The immune response has two main branches: the humoral immune system (mediated by antibodies, targeting extracellular threats) and the cellular immune system (mediated by T cells, destroying infected or abnormal host cells).
Antibodies (Immunoglobulins): Structure and Classes
• Antibodies (immunoglobulins, Ig) are soluble proteins produced by B lymphocytes that bind to foreign molecules (antigens) and target them for destruction.
• IgG is the most abundant class, with two heavy and two light polypeptide chains arranged in a Y-shape and linked by disulfide and noncovalent bonds.
• Each IgG molecule has two identical antigen-binding sites formed by the variable domains of one heavy and one light chain; these regions are hypervariable, enabling diversity and specificity.
• The structure of immunoglobulins features constant domains (immunoglobulin fold) and variable domains responsible for antigen recognition.
• There are five main classes of immunoglobulins (IgA, IgD, IgE, IgG, IgM), each with distinct heavy chains, structures, and biological roles (e.g., IgA in secretions, IgM as a pentamer, IgE in allergies).
• IgM is the first antibody made in an immune response; IgG is most abundant in secondary responses and in blood.
Immune System Function and Memory
• T lymphocytes (T cells) express receptors (T-cell receptors) that recognize infected or abnormal cells and mediate cellular immune responses (e.g., cytotoxic T cells directly kill infected cells; helper T cells release cytokines).
• Helper T cells stimulate selective proliferation of B and T cells that can bind a particular antigen (clonal selection), and memory cells ensure rapid secondary responses to previously encountered pathogens (basis of vaccination).
• HIV targets and destroys helper T cells, crippling the immune response.
Antigen Recognition, Epitopes, and Haptens
• An antigen is any molecule capable of eliciting an immune response; antibodies or T-cell receptors bind to specific regions (epitopes) on the antigen.
• Small molecules not normally antigenic can become so when covalently linked to larger proteins (haptens); antibodies raised against hapten-protein complexes can bind free haptens.
Antibody-Antigen Binding: Mechanism and Specificity
• Binding specificity is determined by the precise chemical complementarity of the antigen-binding site (variable domains) and the epitope.
• The binding site can undergo conformational changes (induced fit) upon antigen binding to optimize interaction—driven by hydrogen bonds, ionic interactions, van der Waals forces, and the hydrophobic effect.
• Antibody-antigen interactions are very strong (low Kd values), providing the high specificity and sensitivity exploited in analytical assays.
Analytical Applications: Polyclonal and Monoclonal Antibodies
• Polyclonal antibodies are mixtures produced by multiple B cell clones against different epitopes of an antigen; monoclonal antibodies are produced by a single B cell clone, recognizing one epitope.
• Antibodies are widely used as analytical tools—for example, in immunoblotting (Western blot), where antibodies detect and quantify proteins in complex samples.
• Labeled antibodies allow visualization of specific proteins in gels, membranes, or cells, greatly aiding research and diagnostics.
In a Nutshell
• The immune system uses a sophisticated array of proteins (antibodies, receptors) to recognize, bind, and eliminate pathogens via highly specific protein-ligand interactions.
• Immunoglobulins (antibodies) are structurally diverse and specialized, with variable domains enabling precise recognition of antigens.
• Antibody specificity and high affinity form the basis of powerful analytical methods such as immunoblotting, with major applications in research, diagnostics, and medicine.