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Immunoglobulin: Isotypes, Allotypes and Idiotypes

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. Reacts with IgM, IgG, IgA, IgD, IgE. ??.

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Immunoglobulin: Isotypes, Allotypes and Idiotypes

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  1. Immunoglobulin:Isotypes, Allotypes and Idiotypes

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

  3. Immunoglobulin Isotypes Human IgM Reacts with IgM, IgG, IgA, IgD, IgE ?? antiserum React with IgG, IgA, IgD and IgE Absorbed antiserum Reacts only with IgM Recognizes determinants specific for µ heavy chains (isotypes)

  4. IgG1 (kappa) IgM (kappa) Immunoglobulin Isotypes • Definition • Occurrence • Importance • Ig levels • B cell tumors • Immunodeficiencies • Location VH VL CH1 CH2 CH3 + CH4 Isotypic variation is present in the germline of all members of a species producing the heavy(μ,δ,γ,ε,α) and light chains (Igκ,λ) and the V region framework

  5. IgG1 (kappa) Person 1 IgG1 (kappa) Person 2 Immunoglobulin Allotypes • Definition - Antigenic determinants specified • by allelic forms of the Ig genes • Source of anti-allotypic Abs • Location • Occurrence

  6. Human Immunoglobulin Allotypes • Nomenclature • G1m(3) • Km(1) • Definition of the • heavy chain class • followed by sub- • class, an “m” • for marker, and • the designated • number or letter in • brackets • In humans allotypes are encountered • within: IgG; IgA and κ light chains • All heavy chain genes are encoded • within the same locus, they are • inherited as a complex or haplotype

  7. 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

  8. Human Immunoglobulin Allotypes • Genetics (pseudoalleles) • Co-dominant G1m(17) G1m(1) 214 355-358

  9. Immunoglobulin Allotypes • Definition • Location • Occurrence • Importance • Monitoring bone marrow grafts • Forensic medicine • Paternity testing

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

  11. Immunoglobulin Idiotypes Strain A Mouse Anti-DNP Ab DNP-BSA Ab against combining site of anti-DNP Ab Strain A Mouse Purified anti-DNP Ab Antigenic determinants created by the HVR = Idiotypes

  12. 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

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

  14. 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 patient’s genetic background, the Disease treated, dosing regimen, etc.

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

  16. + + Ag Id anti-Id Ag Id anti-Id - Anti-Idiotype Vaccines In some cases anti-idiotypic antibodies stimulate B cells to make antibody. This approach can be used as a vaccine

  17. 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 Díaz*, Ana María Hernández*, Alexis Pérez*, Edmundo Rodríguez, Roberto Bitton, Rolando Pérez* and Ana María Vázquez** 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

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

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