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Lecture 13 Antigens, Receptors and Immunoglobulins. Antigenic Determinants (Epitopes). Receptor-Epitope Concepts. Most biological systems can be viewed in terms of interactions between receptors and epitopes (“hand and glove”).
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Receptor-Epitope Concepts • 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…
Examples of Receptor-Epitope Interactions • Enzymatic reactions • Antigen recognition • Antigen-Antibody reactions • Biological chaperones (stress proteins) • Cellular communications • Cell-mediated cytotoxicity • Cellular homing (MALT, chemotaxis, etc.)
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
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
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
Immunoglobulin A (IgA) • Monomeric- Serum IgA • ~15-20% of serum immunoglobulins • 2 Heavy and 2 Light • 2 Subclasses (IgA1 and IgA2) • Found in serum
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
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
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
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?