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Immunoglobulin:

Isotypes, Allotypes and Idiotypes

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Immunoglobulin Isotypes

Definition - Antigenic determinants that

characterize the classes and subclasses of

heavy chains and types and subtypes oflight chains

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Human IgM

antiserumReacts with

IgM, IgG, IgA, IgD, IgE

React with IgG, IgA, IgD and IgE

Absorbed antiserum Reacts only with IgM

Recognizes determinants

specific for heavy chains

(isotypes)

Immunoglobulin Isotypes

??

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Immunoglobulin Isotypes

Occurrence

Importance

Ig levels

B cell tumors

Immunodeficiencies

Definition

Location

IgM (kappa)IgG1 (kappa)

CH1

CH2

CH3 + CH4

VH

VL

Isotypic variation is present in the germline of all members of a

species producing the heavy(,,,,) and light chains (Ig,) and

the V region framework

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Immunoglobulin Allotypes

Definition - Antigenic determinants specified

by allelic forms of the Ig genes

Location

Occurrence

Source of anti-allotypic Abs

IgG1 (kappa)

Person 2

IgG1 (kappa)

Person 1

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Human Immunoglobulin Allotypes

Nomenclature

G1m(3)

Km(1)

Definition of the

heavy chain class

followed by sub-

class, an m

for marker, and

the designatednumber or letter in

brackets

Chain Domain AllotypeAminoAcid

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

In humans allotypes are encounteredwithin: IgG; IgA and light chains

All heavy chain genes are encoded

within the same locus, they are

inherited as a complex or haplotype

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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 AllotypeAminoAcid

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

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Chain Domain AllotypeAminoAcid

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, 191light

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

Genetics

(pseudoalleles)

Co-dominant

G1m(17) G1m(1)

214 355-358

Human Immunoglobulin Allotypes

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Immunoglobulin Allotypes

Definition

Location

Occurrence

Importance

Monitoring bone marrow grafts

Forensic medicine

Paternity testing

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Immunoglobulin Idiotypes

Definition - Unique antigenic determinants

present on individual antibody molecules or

on molecules of identical specificity

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DNP-BSAStrain A

MouseAnti-DNP Ab

Purified

anti-DNP Ab

Strain A

Mouse

Ab against

combining site of

anti-DNP Ab

Immunoglobulin Idiotypes

Antigenic

determinants

created by the

HVR = Idiotypes

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Immunoglobulin Idiotypes

Definition

Location

IgG1 (kappa)

Person 1

anti-B

IgG1 (kappa)

Person 1

anti-A

Idiotypes are localized

on the Fab fragment

specifically at or near

the HVR of heavy andlight chains

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Immunoglobulin Idiotypes

Definition

Location

Importance

V region marker

Regulation of immune responses

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Ag Id anti-Id

+

-

anti-anti-Id

+

-

Regulation by Id/anti-Id

Each therapeutic antibody is structurally unique and has thepotential to provoke immune response in the recipients.

These antibodies are called anti-idiotypic antibodies and their

Generation depends on the patients genetic background, the

Disease treated, dosing regimen, etc.

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Immunoglobulin Idiotypes

Definition

Location

Importance

V region marker

Regulation of immune responses

Vaccines

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Ag Id anti-Id

+

-

Anti-Idiotype Vaccines

Ag Id anti-Id

+

In some cases anti-idiotypic antibodies stimulateB cells to make antibody. This approach can be

used as a vaccine

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Example of an Anti-Idiotype Vaccine

The Journal of Immunology, 2002, 168: 2523-2529.

An Anti-Idiotype Vaccine Elicits a Specific

Response to N-Glycolyl Sialic Acid Residues ofGlycoconjugates in Melanoma Patients1

Mauro Alfonso2,*, Alain Daz*, Ana Mara Hernndez*, Alexis Prez*,

Edmundo Rodrguez, Roberto Bitton, Rolando Prez*and Ana Mara

Vzquez

*

*

Center of Molecular Immunology and National Institute ofOncology and Radiobiology, Havana, Cuba; and ELEA Laboratories,

Buenos Aires, Argentina

Vaccine was safe and produced the desired antibodies in 16 of 17 patients

http://www.jimmunol.org/cgi/content/full/168/5/2523http://www.jimmunol.org/cgi/content/full/168/5/2523http://www.jimmunol.org/cgi/content/full/168/5/2523http://www.jimmunol.org/cgi/content/full/168/5/2523

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Immunoglobulin Idiotypes

Definition

Location

Importance

V region marker

Regulation of immune responses

Vaccines

Treatment of B cell tumors (T cell)