Lecture 2 Antigens, Receptors and Immunoglobulins

Antigenic Determinants (Epitopes)

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

Receptor-Epitope Interactions and Affinity Most biological systems can be viewed in terms of interactions between receptors and epitopes (“hand and glove”). 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”). 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 big, the glove falls off. If the glove is too small, you can’t get your hand into it. If the glove is too small, you can’t get your hand into it. If the glove is missing fingers… If the glove is missing fingers…

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

Basic Immunoglobulin Structure

The Prototype Immunoglobulin Molecule Fab Fc VHVH C H1 C H2 C H3 VLVL CLCL Heavy Chains (five types:  Heavy Chains (five types:  Light Chains (two types:  and  Light Chains (two types:  and  Fab fragment Fab fragment Fc fragment Fc fragment Constant and variable regions Constant and variable regions Carbohydrate Carbohydrate Disulfide linkages Disulfide linkages

Immunoglobulin G (IgG) 2 Heavy and 2 Light chains 2 Heavy and 2 Light chains 2 Fab and 1 Fc fragment 2 Fab and 1 Fc fragment 4 Subclasses (IgG1, IgG2, IgG3, IgG4) 4 Subclasses (IgG1, IgG2, IgG3, IgG4) Mol. Wt. 150,000 Mol. Wt. 150,000 ~70-75% of serum immunoglobulin. ~70-75% of serum immunoglobulin. The major antibody of the secondary immune response The major antibody of the secondary immune response Change in affinity with time Change in affinity with time Fab Fc VHVH C H1 C H2 C H3 VLVL CLCL

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

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

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

Immunoglobulin E (IgE) 2 Heavy and 2 Light chains 2 Heavy and 2 Light chains Mol. Wt. ~190,000 Mol. Wt. ~190,000 Trace serum protein Trace serum protein Note CH4 region on H chain Note CH4 region on H chain Associated with atopic or anaphylactic hypersensitivity Associated with atopic or anaphylactic hypersensitivity May play role in immunity to helminthic parasites May play role in immunity to helminthic parasites C H4

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

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