4. Ig Structure and Function 2

8/10/2019 4. Ig Structure and Function 2

1/46

Antibody: Structure and

Function


2/46

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

Amountofprotein


3/46

B Cells

work chiefly by secreting

soluble substances knownas antibodies (Ab)


4/46

General Functions of

Immunoglobulins: What do Ab do?

Effector functions

Fixation of complement

Binding to various cells

(Usually require Ag binding)

Ag binding

Can result in protection

Valency


5/46


6/46

Basic Immunoglobulin Structure

Immunoglobulins - heterogeneous

Myeloma proteins - homogeneous

immunoglobulins


7/46

Immunoglobulin Structure

Heavy & Light

Chains

Disulfide bonds Inter-chain

Intra-chain

CH1

VL

CL

VH

CH2 CH3

Hinge Region

Carbohydrate

Disulfide bond


8/46

Immunoglobulin Structure

Variable &

ConstantRegions

VL& CL

VH& CH

Hinge Region

CH1

VL

CL

VH

CH2 CH3

Hinge Region

Carbohydrate

Disulfide bond


9/46


10/46

IgG molecule

Used with permission from: Dr. Mike Clark, Immunology

Division, Department of Pathology Cambridge University,

Cambridge, England


11/46

Structure of the Variable Region

Hypervariable (HVR) or complimentaritydetermining regions (CDR)

HVR3

FR1 FR2 FR3 FR4

HVR1HVR2

VariabilityIndex

25 7550 100Amino acid residue

150

100

50

0

Framework regions


12/46

Immunoglobulin Fragments:

Structure/Function Relationships

Fab

Ag binding

Valence = 1

Specificty

determined by VH

and VL

Papain

Fc

Fab

Fc

Effector

functions


13/46

Immunoglobulin Fragments:

Structure/Function Relationships

Ag Binding

Complement Binding Site

Placental Transfer

Binding to Fc

Receptors


14/46


15/46


16/46


17/46


18/46

Immunoglobulin (Ig) domains (also called

Ig folds) occur as repeating structural units

in many molecules, including antibodies,

the T cell antigen receptor, cytokinereceptors (e.g. the platelet-derived growth

factor receptor with 5 Ig domains), cell

adhesion molecules (e.g. ICAM-1/CD54),and many others.


19/46

Human Immunoglobulin Classes

IgG - Gamma () heavy chains

IgM - Mu () heavy chains

IgA - Alpha (

) heavy chains IgD - Delta () heavy chains

IgE - Epsilon () heavy chains


20/46

Human Immunoglobulin

Subclasses

IgG Subclasses

IgG1 - Gamma 1 (1) heavy chains




IgA subclasses

IgA1 - Alpha 1 (1) heavy chains

IgA2 - Alpha 2 (2) heavy chains


21/46


Light Chain Types

Kappa ()

Lambda ()


22/46


Light Chain Subtypes

Lambda light chains

Lambda 1 (1)

Lambda 2 (2) Lambda 3 (3)

Lambda 4 (4)


23/46

Immunoglobulins

Nomenclature

IgM (kappa)

IgA1(lambda 2)

IgG

Heterogeneity


24/46


25/46

IgG

Structure

Properties

Major serum Ig Major Ig in extravascular spaces

Placental transfer Does not require Agbinding (IgG2)

Fixes complement (IgG4)

Binds to Fc receptors (IgG2, IgG4) Phagocytes - opsonization

K cells - ADCC


26/46

IgM

Structure

Pentamer (19S)

Extra domain(CH4)

J chain C4

J Chain


27/46

IgM

Structure

Properties

3rd highest serum Ig First Ig made by

fetus and B cells

Fixes complement


28/46


29/46

IgM

Structure

Properties

3rd highest serum Ig First Ig made by

fetus and B cells

Fixes complement

Tail

Piece

Agglutinating Ig

Binds to Fc

receptors

B cell surface Ig


30/46

B Cell Antigen Receptor (BcR)

Ig-Ig- Ig-Ig-


31/46

IgA

Structure Serum - monomer

Secretions (sIgA)

Dimer J chain

Secretory

component

J ChainSecretory Piece

Origin of Secretory Component of


32/46

Origin of Secretory Component of

sIgA


33/46

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


34/46

IgD

Structure

Monomer

Tail piece

Tail Piece


35/46

IgD

Structure

Properties

4th highest serum Ig

B cell surface Ig

Does not bind complement


36/46

IgE

Structure

Monomer

Extra domain(CH4)

C 4


37/46

IgE

Structure

Properties

Least common serum Ig

Binds to basophils and mast cells (Does notrequire Ag binding)

Allergic reactions

Parasitic infections (Helminths)

Binds to Fc receptor on eosinophils

Does not fix complement


38/46

Immunoglobulin:

Isotypes, Allotypes and Idiotypes


39/46

Immunoglobulin Isotypes

Definition - Antigenic determinants that

characterize the classes and subclasses

of heavy chains and types and subtypes of

light chains


40/46

Immunoglobulin Isotypes

Occurrence

Importance

Ig levels

B cell tumors

Immunodeficienci

es

Definition

Location

IgM (kappa)IgG1 (kappa)


41/46

Immunoglobulin Allotypes

Definition - Antigenic determinants specified

by allelic forms of the Ig genes

Location

Occurrence

IgG1 (kappa)

Person 2

IgG1 (kappa)

Person 1


42/46

Human Immunoglobulin Allotypes

Nomenclature

G1m(3)

Km(1)

Chain Domain Allotype Amino Acid

Position

CH1 G1m(f) = (3) Arg 214

CH1 G1m(z) = (17) Lys 214

IgG1

CH3 G1m(a) = (1) Arg, Asp,Glu, Leu

355-358

CL Km(1) Val, Leu 153, 191

light

chain CL Km(3) Ala, Val 153, 191


43/46

Human Immunoglobulin Allotypes

Genetics (alleles)

Co-dominant

autosomal genes

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

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

Allelic exclusion

Chain Domain Allotype Amino Acid

Position

CH1 G1m(f) = (3) Arg 214

CH1 G1m(z) = (17) Lys 214

IgG1

CH3 G1m(a) = (1) Arg, Asp,Glu, Leu

355-358

CL Km(1) Val, Leu 153, 191

light

chain CL Km(3) Ala, Val 153, 191


44/46

Immunoglobulin Allotypes

Definition

Location

Occurrence Importance

Monitoring bone marrow grafts

Forensic medicine Paternity testing


45/46

Immunoglobulin Idiotypes

Definition - Unique antigenic determinants

present on individual antibody molecules

or on molecules of identical specificity


46/46

Immunoglobulin Idiotypes

Definition

Location

IgG1 (kappa)

Person 1

anti-B

IgG1 (kappa)

Person 1

anti-A

4. Ig Structure and Function 2

Documents

Transcript of 4. Ig Structure and Function 2