Immunoglobulins:Structure and Function

Aulanni’amBiochemistry Laboratory

Faculty of Sciences_UB

Immunoglobulins:Structure and Function

Definition: Glycoprotein molecules that are produced by plasma cells in response to an immunogen and which function as antibodies

Immune serum

Ag adsorbed serum

1 2

+ -albumin

globulins

Mobility

Am

oun

t of

pro

tein

General Functions of Immunoglobulins

Effector functions Fixation of

complementBinding to various

cells

(Usually require Ag binding)

• Ag binding– Can result in protection

Basic Immunoglobulin Structure

Immunoglobulins - heterogeneous

Myeloma proteins - homogeneous immunoglobulins

Immunoglobulin Structure

Heavy & Light Chains

Disulfide bondsInter-chainIntra-chain

CH1

VL

CL

VH

CH2 CH3

Hinge Region

Carbohydrate

Disulfide bond

Immunoglobulin Structure

Variable & Constant RegionsVL & CL

VH & CH

Hinge RegionCH1

VL

CL

VH

CH2 CH3

Hinge Region

Carbohydrate

Disulfide bond

Immunoglobulin Structure

DomainsVL & CL

VH & CH1 - CH3 (or CH4)

Oligosaccharides

CH1

VL

CL

VH

CH2 CH3

Hinge Region

Carbohydrate

Disulfide bond

IgG molecule

Structure of the Variable Region

Hypervariable (HVR) or complimentarity determining regions (CDR)

HVR3

FR1 FR2 FR3 FR4

HVR1HVR2

Var

iabi

lity

Ind

ex

25 7550 100Amino acid residue

150

100

50

0

Framework regions

Immunoglobulin Fragments: Structure/Function Relationships

FabAg bindingValence = 1Specificty

determined by VH and VL

Papain

Fc

Fab

FcEffector functions

Immunoglobulin Fragments: Structure/Function Relationships

Ag Binding

Complement Binding Site

Placental Transfer

Binding to Fc Receptors

Immunoglobulin Fragments: Structure/Function Relationships

FabAg binding

FcEffector functions

F(ab’)2

Pepsin

Fc Peptides

F(ab’)2

Human Immunoglobulin Classes

IgG - Gamma () heavy chains

IgM - Mu () heavy chainsIgA - Alpha () heavy chainsIgD - Delta () heavy chainsIgE - Epsilon () heavy chains

Human Immunoglobulin Subclasses IgG Subclasses

IgG1 - Gamma 1 (1) heavy chainsIgG2 - Gamma 2 (2) heavy chainsIgG3 - Gamma 3 (3) heavy chainsIgG4 - Gamma 4 (4) heavy chains

IgA subclassesIgA1 - Alpha 1 (1) heavy chainsIgA2 - Alpha 2 (2) heavy chains

Human ImmunoglobulinLight Chain Types

Kappa ()Lambda ()

Human ImmunoglobulinLight Chain Subtypes

Lambda light chainsLambda 1 (1)Lambda 2 (2)Lambda 3 (3) Lambda 4 (4)

Immunoglobulins

NomenclatureIgM (kappa)IgA1(lambda 2)IgG

Heterogeneity

IgG

StructureMonomer (7S)

IgG1, IgG2 and IgG4 IgG3

IgGStructureProperties

Major serum IgMajor Ig in extravascular spacesPlacental transfer – Does not require Ag

binding ( IgG2)Fixes complement ( IgG4)Binds to Fc receptors ( IgG2, IgG4)

Phagocytes - opsonizationK cells - ADCC

IgM

StructurePentamer (19S)Extra domain (CH4)

J chainC4

J Chain

IgM

StructureProperties

3rd highest serum IgFirst Ig made by fetus

and B cellsFixes complement

Fixation of C1 by IgG and IgM Abs

C1r C1s

C1qC1r C1s

C1q

No activation Activation

IgM

StructureProperties

3rd highest serum IgFirst Ig made by fetus

and B cellsFixes complement

Tail Piece

Agglutinating IgBinds to Fc receptorsB cell surface Ig

B Cell Antigen Receptor (BcR)

Ig-Ig- Ig-Ig-

IgA

StructureSerum - monomerSecretions (sIgA)

Dimer (11S)J chainSecretory

component

J ChainSecretory Piece

IgA

StructureProperties

2nd highest serum IgMajor secretory Ig (Mucosal or Local Immunity)

Tears, saliva, gastric and pulmonary secretions

Does not fix complement (unless aggregated)Binds to Fc receptors on some cells

IgD

StructureMonomerTail piece

Tail Piece

IgD

StructureProperties

4th highest serum IgB cell surface IgDoes not bind complement

IgE

StructureMonomerExtra domain (CH4)

C4

IgE

StructureProperties

Least common serum IgBinds to basophils and mast cells (Does not

require Ag binding)Allergic reactionsParasitic infections (Helminths)

Binds to Fc receptor on eosinophilsDoes not fix complement