1. Lecture 2Antigens, Receptors and Immunoglobulins

2. Antigenic Determinants (Epitopes)

3. What is an antibody? • Product of adaptive immunity • Made specifically to bind a unique antigenic epitope (also called an antigenic determinant) • Possesses an antigen binding site • A product of the Plasma cell • Members of the class of proteins called immunoglobulins

4. Receptor-Epitope Interactions and Affinity • Most biological systems can be viewed in terms of interactions between receptors and epitopes (“hand and glove”). • Specificity of the interaction between the receptor and epitope is determined by the amino acid sequence of the receptor (“tailoring the glove”). • If the glove is too big, the glove falls off. • If the glove is too small, you can’t get your hand into it. • If the glove is missing fingers…

5. POOR FIT high repulsion high attraction low attraction low repulsion Binding of the epitope in the antigen binding site GOOD FIT antibody combining site antigen determinant

6. Basic Immunoglobulin Structure

7. The Prototype Immunoglobulin Molecule Fab • Heavy Chains (five types:  • Light Chains (two types: and • Fab fragment • Fc fragment • Constant and variable regions • Carbohydrate • Disulfide linkages VH VL CH1 CL CH2 Fc CH3

8. Fab VH VL CH1 CL CH2 Fc CH3 Immunoglobulin G (IgG) • 2 Heavy and 2 Light chains • 2 Fab and 1 Fc fragment • 4 Subclasses (IgG1, IgG2, IgG3, IgG4) • Mol. Wt. 150,000 • ~70-75% of serum immunoglobulin. • The major antibody of the secondary immune response • Change in affinity with time

9. J-Chain Immunoglobulin M (IgM) • 10 Heavy and 10 Light chains • 10 Fab and 5 Fc fragments • Mol. Wt. ~900,000 • <10% of serum immunoglobulin. • Single J Chain (15 kDA) • The predominant "early" antibody • Most primitive immunoglobulin • No change in affinity with time

10. Immunoglobulin A (IgA) • Monomeric- Serum IgA • ~15-20% of serum immunoglobulins • 2 Heavy and 2 Light • 2 Subclasses (IgA1 and IgA2) • Found in serum

11. Secretory Immunoglobulin A (sIgA) J-Chain • 4 heavy chains and 4 light chains (dimeric) • J-Chain and secretory component • The major immunoglobulin of secretions • Not found in serum Secretory Component

12. Immunoglobulin E (IgE) • 2 Heavy and 2 Light chains • Mol. Wt. ~190,000 • Trace serum protein • Note CH4 region on H chain • Associated with atopic or anaphylactic hypersensitivity • May play role in immunity to helminthic parasites CH4

13. Immunoglobulin D (IgD) • 2 heavy and 2 light chains • <1% of serum immunoglobulins • Serves as a membrane receptor on B lymphocytes • May play role in antigen-stimulated lymphocyte differentiation

14. Take Home Lessons • What is the basic immunoglobulin structure? • What are the characteristics or features of the various fragments of the immunoglobulin molecule? • How is the specificity of an antibody “defined” by the amino acid sequence of the immunoglobulin molecule? • What features distinguish each immunoglobulin class?