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Antibody: Structure and

Function

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

Amount of protein

albumin
globulins

Immune serum
Ag adsorbed serum

Mobility

B Cells
work chiefly by secreting
soluble substances known
as antibodies (Ab)

General Functions of
Immunoglobulins: What do Ab do?
Ag binding
Can result in protection
Valency

Effector functions (Usually require Ag binding)


Fixation of complement
Binding to various cells

Basic Immunoglobulin Structure


Immunoglobulins - heterogeneous
Myeloma proteins - homogeneous
immunoglobulins

Immunoglobulin Structure
Heavy & Light
Chains
Disulfide bonds
Inter-chain
Intra-chain

Disulfide bond

Carbohydrate

CL
VL
CH2

CH1
VH

Hinge Region

CH3

Immunoglobulin Structure
Disulfide bond

Variable &
Constant
Regions
VL & CL
VH & CH

Hinge Region

Carbohydrate

CL
VL
CH2

CH1

VH

Hinge Region

CH3

Immunoglobulin Structure
Domains

Disulfide bond

VL & CL
VH & CH1 - CH3
(or CH4)

Oligosaccharides

Carbohydrate

CL
VL
CH2

CH1

VH

Hinge Region

CH3

IgG molecule

Used with permission from: Dr. Mike Clark, Immunology


Division, Department of Pathology Cambridge University,
Cambridge, England

Structure of the Variable Region

Variability Index

Hypervariable (HVR) or complimentarity


determining regions (CDR)
HVR3
150

100

HVR2

HVR1
50

FR2

FR1

25

FR3

75
50
Amino acid residue

Framework regions

FR4

100

Immunoglobulin Fragments:
Structure/Function Relationships
Fab

Papain

Ag binding
Valence = 1
Specificty
determined by VH
and VL

Fc
Effector
functions

Fc
Fab

Immunoglobulin Fragments:
Structure/Function Relationships
Ag Binding

Complement Binding Site


Binding to Fc
Receptors
Placental Transfer

Immunoglobulin Fragments:
Structure/Function Relationships
Fab

Pepsin

Ag binding

Fc
Effector functions

F(ab)2
Fc
Peptides
F(ab)2

Immunoglobulin (Ig) domains (also called


Ig folds) occur as repeating structural units
in many molecules, including antibodies,
the T cell antigen receptor, cytokine
receptors (e.g. the platelet-derived growth
factor receptor with 5 Ig domains), cell
adhesion molecules (e.g. ICAM-1/CD54),
and many others.

Human Immunoglobulin Classes

IgG - Gamma () heavy chains


IgM - Mu () heavy chains
IgA - Alpha () heavy chains
IgD - Delta () heavy chains
IgE - Epsilon () heavy chains

Human Immunoglobulin
Subclasses
IgG Subclasses
IgG1 - Gamma 1 (1) heavy chains
IgG2 - Gamma 2 (2) heavy chains
IgG3 - Gamma 3 (3) heavy chains
IgG4 - Gamma 4 (4) heavy chains

IgA subclasses
IgA1 - Alpha 1 (1) heavy chains
IgA2 - Alpha 2 (2) heavy chains

Human Immunoglobulin
Light Chain Types
Kappa ()
Lambda ()

Human Immunoglobulin
Light Chain Subtypes
Lambda light chains
Lambda 1 (1)
Lambda 2 (2)
Lambda 3 (3)
Lambda 4 (4)

Immunoglobulins
Nomenclature
IgM (kappa)
IgA1(lambda 2)
IgG

Heterogeneity

IgG
Structure
Monomer

IgG1, IgG2 and IgG4

IgG3

IgG
Structure
Properties
Major serum Ig
Major Ig in extravascular spaces
Placental transfer Does not require Ag
binding ( IgG2)
Fixes complement ( IgG4)
Binds to Fc receptors ( IgG2, IgG4)
Phagocytes - opsonization
K cells - ADCC

IgM
Structure
Pentamer (19S)
Extra domain
(CH4)
J chain

J Chain

C4

IgM
Structure
Properties
3rd highest serum Ig
First Ig made by
fetus and B cells
Fixes complement

Fixation of C1 by IgG and IgM Abs

No activation

Activation

IgM
Structure
Properties
3rd highest serum Ig
First Ig made by
fetus and B cells
Fixes complement
Agglutinating Ig
Binds to Fc
receptors
B cell surface Ig

Tail
Piece

B Cell Antigen Receptor (BcR)

Ig- Ig-

Ig- Ig-

IgA
Structure
Serum - monomer
Secretions (sIgA)
Dimer
J chain
Secretory
component

Secretory Piece

J Chain

Origin of Secretory Component of


sIgA

IgA
Structure
Properties
2nd highest serum Ig
Major secretory Ig (Mucosal or Local Immunity)
Tears, saliva, gastric and pulmonary secretions

Does not fix complement


Binds to Fc receptors on some cells

IgD
Structure
Monomer
Tail piece
Tail Piece

IgD
Structure
Properties
4th highest serum Ig
B cell surface Ig
Does not bind complement

IgE
Structure
Monomer
Extra domain
(CH4)

C4

IgE
Structure
Properties
Least common serum Ig
Binds to basophils and mast cells (Does not
require Ag binding)

Allergic reactions
Parasitic infections (Helminths)
Binds to Fc receptor on eosinophils

Does not fix complement

Immunoglobulin:
Isotypes, Allotypes and Idiotypes

Immunoglobulin Isotypes
Definition - Antigenic determinants that
characterize the classes and subclasses
of heavy chains and types and subtypes of
light chains

Immunoglobulin Isotypes
Definition
Location
Occurrence
Importance
Ig levels
B cell tumors
Immunodeficienci
es

IgG1 (kappa)

IgM (kappa)

Immunoglobulin Allotypes
Definition - Antigenic determinants specified
by allelic forms of the Ig genes

Location

Occurrence
IgG1 (kappa)

IgG1 (kappa)

Person 1

Person 2

Human Immunoglobulin Allotypes


Nomenclature
G1m(3)
Km(1)

Domain

IgG1

CH1

G1m(f) = (3)

Arg

214

CH1

G1m(z) = (17) Lys

214

CH3

G1m(a) = (1)

355-358

CL

Km(1)

Arg, Asp,
Glu, Leu
Val, Leu

CL

Km(3)

Ala, Val

153, 191

light
chain

Allotype

Amino
Acid

Chain

Position

153, 191

Human Immunoglobulin Allotypes


Genetics (alleles)
Co-dominant
autosomal genes

Domain

IgG1

CH1

G1m(f) = (3)

Arg

214

CH1

G1m(z) = (17) Lys

214

CH3

G1m(a) = (1)

355-358

CL

Km(1)

Arg, Asp,
Glu, Leu
Val, Leu

CL

Km(3)

Ala, Val

153, 191

Km(1)/Km(3) X Km(1)/Km(1)

Km(1)/Km(1) and Km(1)/Km(3)

Allelic exclusion

light
chain

Allotype

Amino
Acid

Chain

Position

153, 191

Immunoglobulin Allotypes

Definition
Location
Occurrence
Importance
Monitoring bone marrow grafts
Forensic medicine
Paternity testing

Immunoglobulin Idiotypes
Definition - Unique antigenic determinants
present on individual antibody molecules
or on molecules of identical specificity

Immunoglobulin Idiotypes
Definition
Location

IgG1 (kappa)

IgG1 (kappa)

Person 1

Person 1

anti-A

anti-B