Lecture 2Lecture 2Antigens, Receptors and Antigens, Receptors and

ImmunoglobulinsImmunoglobulins

Antigenic Determinants (Epitopes)Antigenic Determinants (Epitopes)

What is an antibody?What is an antibody?

Product of adaptive immunityProduct of adaptive immunity Made specifically to bind a unique antigenic Made specifically to bind a unique antigenic

epitope (also called an antigenic epitope (also called an antigenic determinant)determinant)

Possesses an antigen binding sitePossesses an antigen binding site A product of the Plasma cellA product of the Plasma cell Members of the class of proteins called Members of the class of proteins called

immunoglobulinsimmunoglobulins

Receptor-Epitope Interactions and Receptor-Epitope Interactions and AffinityAffinity

Most biological systems can be viewed in terms of Most biological systems can be viewed in terms of interactions between receptors and epitopes interactions between receptors and epitopes (“hand and glove”).(“hand and glove”).

Specificity of the interaction between the receptor Specificity of the interaction between the receptor and epitope is determined by the amino acid and epitope is determined by the amino acid sequence of the receptor (“tailoring the glove”).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 Binding of the epitope in the antigen binding sitethe antigen binding site

POOR FITGOOD FIT

antibody combining site

antigen determinant

high attractionlow repulsion

high repulsionlow attraction

Basic Immunoglobulin StructureBasic Immunoglobulin Structure

The Prototype Immunoglobulin The Prototype Immunoglobulin MoleculeMolecule

Fab

Fc

VH

CH1

CH2

CH3

VL

CL

Heavy Chains (five Heavy Chains (five types: types:

Light Chains (two Light Chains (two types: types: andand

Fab fragmentFab fragment Fc fragmentFc fragment Constant and Constant and

variable regionsvariable regions CarbohydrateCarbohydrate Disulfide linkagesDisulfide linkages

Immunoglobulin G (IgG)Immunoglobulin G (IgG)

2 Heavy and 2 Light chains2 Heavy and 2 Light chains 2 Fab and 1 Fc fragment2 Fab and 1 Fc fragment 4 Subclasses (IgG1, IgG2, 4 Subclasses (IgG1, IgG2,

IgG3, IgG4)IgG3, IgG4) Mol. Wt. 150,000 Mol. Wt. 150,000 ~70-75% of serum ~70-75% of serum

immunoglobulin.immunoglobulin. The major antibody of the The major antibody of the

secondary immune responsesecondary immune response Change in affinity with timeChange in affinity with time

Fab

Fc

VH

CH1

CH2

CH3

VL

CL

Immunoglobulin M (IgM)Immunoglobulin M (IgM)

10 Heavy and 10 Light chains10 Heavy and 10 Light chains 10 Fab and 5 Fc fragments10 Fab and 5 Fc fragments Mol. Wt. ~900,000Mol. Wt. ~900,000 <10% of serum <10% of serum

immunoglobulin.immunoglobulin. Single J Chain (15 kDA)Single J Chain (15 kDA) The predominant "early" The predominant "early"

antibodyantibody Most primitive immunoglobulinMost primitive immunoglobulin No change in affinity with timeNo change in affinity with time

J-Chain

Immunoglobulin A (IgA)Immunoglobulin A (IgA)

Monomeric- Serum Monomeric- Serum IgAIgA

~15-20% of serum ~15-20% of serum immunoglobulinsimmunoglobulins

2 Heavy and 2 Light 2 Heavy and 2 Light 2 Subclasses (IgA1 2 Subclasses (IgA1

and IgA2)and IgA2) Found in serumFound in serum

Secretory Immunoglobulin A Secretory Immunoglobulin A (sIgA)(sIgA)

4 heavy chains and 4 light chains (dimeric)4 heavy chains and 4 light chains (dimeric) J-Chain and secretory componentJ-Chain and secretory component The major immunoglobulin of secretionsThe major immunoglobulin of secretions Not found in serumNot found in serum

Secretory Component

J-Chain

Immunoglobulin E (IgE)Immunoglobulin E (IgE)

2 Heavy and 2 Light 2 Heavy and 2 Light chainschains

Mol. Wt. ~190,000 Mol. Wt. ~190,000 Trace serum proteinTrace serum protein Note CH4 region on H Note CH4 region on H

chainchain Associated with atopic or Associated with atopic or

anaphylactic anaphylactic hypersensitivityhypersensitivity

May play role in immunity May play role in immunity to helminthic parasitesto helminthic parasites

CH4

Immunoglobulin D (IgD)Immunoglobulin D (IgD)

2 heavy and 2 light 2 heavy and 2 light chainschains

<1% of serum <1% of serum immunoglobulinsimmunoglobulins

Serves as a membrane Serves as a membrane receptor on B receptor on B lymphocyteslymphocytes

May play role in antigen-May play role in antigen-stimulated lymphocyte stimulated lymphocyte differentiationdifferentiation

Take Home LessonsTake Home Lessons

What is the basic immunoglobulin structure?What is the basic immunoglobulin structure? What are the characteristics or features of the various What are the characteristics or features of the various

fragments of the immunoglobulin molecule?fragments of the immunoglobulin molecule? How is the specificity of an antibody “defined” by the How is the specificity of an antibody “defined” by the

amino acid sequence of the immunoglobulin molecule?amino acid sequence of the immunoglobulin molecule? What features distinguish each immunoglobulin class?What features distinguish each immunoglobulin class?