Immunoglobulin Isotypes Allotypes and Idiotypes Immunoglobulin Isotypes Definition

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 Ig. M antiserum Reacts with Ig. M, Ig. G, Ig. A, Ig. D, Ig. E ? ? React with Ig. G, Ig. A, Ig. D and Ig. E Absorbed antiserum Reacts only with Ig. M Recognizes determinants specific for µ heavy chains (isotypes)

Immunoglobulin Isotypes • • Definition Location Occurrence Importance VH VL – Ig levels – B cell tumors CH 3 + CH 4 – Immunodeficiencies CH 1 CH 2 Ig. G 1 (kappa) Ig. M (kappa) 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

Immunoglobulin Allotypes • Definition - Antigenic determinants specified by allelic forms of the Ig genes – Source of antiallotypic Abs • Location • Occurrence Ig. G 1 (kappa) Person 1 Person 2

Human Immunoglobulin Allotypes • Nomenclature – G 1 m(3) – Km(1) Definition of the heavy chain class followed by subclass, an “m” for marker, and the designated number or letter in brackets • In humans allotypes are encountered within: Ig. G; Ig. A and κ 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) and Km(1)/Km(3) – Allelic exclusion

Human Immunoglobulin Allotypes • Genetics (pseudoalleles) – Co-dominant G 1 m(17) G 1 m(1) 214 355 -358

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 Ig. G 1 (kappa) Person 1 anti-A anti-B

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

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

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

Anti-Idiotype Vaccines + + 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 Patients 1 Mauro Alfonso 2, *, 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

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