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
Human IgM

antiserum
React with IgG, IgA, IgD and IgE

Reacts with IgM, IgG, IgA, IgD, IgE

??

Absorbed antiserum

Reacts only with IgM

Recognizes determinants specific for heavy chains (isotypes)

Immunoglobulin Isotypes
Definition Location Occurrence Importance
VH VL CH1

Ig levels B cell tumors CH3 + CH4 Immunodeficiencies

CH2

IgG1 (kappa)

IgM (kappa)

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

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

Location Occurrence

IgG1 (kappa) Person 1

IgG1 (kappa) Person 2

Human Immunoglobulin Allotypes

Nomenclature G1m(3) Km(1) Definition of the heavy chain class followed by subclass, an m for marker, and the designated number or letter in brackets
Chain IgG1 Domain CH1 CH1 CH3 light chain CL CL Allotype G1m(f) = (3) Amino Acid Arg Position 214 214 355-358 153, 191 153, 191

G1m(z) = (17) Lys G1m(a) = (1) Km(1) Km(3) Arg, Asp, Glu, Leu Val, Leu Ala, Val

In humans allotypes are encountered within: IgG; IgA and light chains All heavy chain genes are encoded within the same locus, they are inherited as a complex or haplotype

Human Immunoglobulin Allotypes

Genetics (alleles) Co-dominant autosomal genes
Km(1)/Km(3) X Km(1)/Km(1)
Chain IgG1 Domain CH1 CH1 CH3 Allotype G1m(f) = (3) Amino Acid Arg Position 214 214 355-358 153, 191 153, 191

G1m(z) = (17) Lys G1m(a) = (1) Km(1) Km(3) Arg, Asp, Glu, Leu Val, Leu Ala, Val

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

Allelic exclusion

light chain

CL CL

Human Immunoglobulin Allotypes

Genetics (pseudoalleles) Co-dominant
G1m(17)
214
Chain IgG1 Domain CH1 CH1 CH3 Allotype G1m(f) = (3) Amino Acid Arg Position 214 214 355-358 153, 191 153, 191

G1m(1)
355-358

G1m(z) = (17) Lys G1m(a) = (1) Km(1) Km(3) Arg, Asp, Glu, Leu Val, Leu Ala, Val

light chain

CL CL

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
DNP-BSA Strain A Mouse Anti-DNP Ab

Ab against combining site of anti-DNP Ab

Strain A Mouse

Purified anti-DNP Ab

Antigenic determinants created by the HVR = Idiotypes

Immunoglobulin Idiotypes
Definition Location
Idiotypes are localized on the Fab fragment specifically at or near the HVR of heavy and light chains

IgG1 (kappa) Person 1 anti-A

IgG1 (kappa)
Person 1 anti-B

Immunoglobulin Idiotypes
Definition Location Importance
V region marker Regulation of immune responses

Regulation by Id/anti-Id
+
Ag Id anti-Id

+
anti-anti-Id

Each therapeutic antibody is structurally unique and has the potential 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.

Immunoglobulin Idiotypes
Definition Location Importance
V region marker Regulation of immune responses Vaccines

Anti-Idiotype Vaccines
+
Ag Id anti-Id Ag Id

+
anti-Id

In some cases anti-idiotypic antibodies stimulate B cells to make antibody. This approach can be used as a vaccine

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 of Glycoconjugates 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 of Oncology and Radiobiology, Havana, Cuba; and ELEA Laboratories, Buenos Aires, Argentina Vaccine was safe and produced the desired antibodies in 16 of 17 patients

Immunoglobulin Idiotypes
Definition Location Importance
V region marker Regulation of immune responses Vaccines Treatment of B cell tumors (T cell)