Immunology (elective) MLIM-101 Prepared by: Dr. Mohamed S. Abdel-Latif Immunoglobulin: Isotypes, Allotypes and Idiotypes Learning Outcome: At this time you should know the following: 1. To explain the structural basis for immunoglobulin isotypes, allotypes and idiotypes. 2. To describe some of the uses of 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 Reacts with IgM, IgG, IgA, IgD, IgE ?? React with IgG, IgA, IgD and IgE Absorbed antiserum ?? only with IgM Reacts Recognizes ?? determinants specific for heavy chains (isotypes) Immunoglobulin Isotypes • • • • Definition Location Occurrence Importance – Ig levels – B cell tumors – Immunodeficiencies IgG1 (kappa) IgM (kappa) Immunoglobulin Allotypes • Definition - Antigenic determinants specified by allelic forms of the Ig genes – Source of antiallotypic Abs • Location • Occurrence IgG1 (kappa) IgG1 (kappa) Person 1 Person 2 Human Immunoglobulin Allotypes • Nomenclature – G1m(3) – Km(1) Domain IgG1 CH1 G1m(f) = (3) Arg 214 CH1 G1m(z) = (17) Lys 214 CH3 G1m(a) = (1) 355-358 CL Km(1) Arg, Asp, Glu, Leu Val, Leu CL Km(3) Ala, Val 153, 191 light chain Allotype Amino Acid Chain Position 153, 191 Human Immunoglobulin Allotypes • Genetics (alleles) – Co-dominant autosomal genes Domain IgG1 CH1 G1m(f) = (3) Arg 214 CH1 G1m(z) = (17) Lys 214 CH3 G1m(a) = (1) 355-358 CL Km(1) Arg, Asp, Glu, Leu Val, Leu CL Km(3) Ala, Val 153, 191 Km(1)/Km(3) X Km(1)/Km(1) Km(1)/Km(1) and Km(1)/Km(3) – Allelic exclusion light chain Allotype Amino Acid Chain Position 153, 191 Human Immunoglobulin Allotypes • Genetics (pseudoalleles) – Co-dominant G1m(17) 214 Domain IgG1 CH1 G1m(f) = (3) Arg 214 CH1 G1m(z) = (17) Lys 214 CH3 G1m(a) = (1) 355-358 CL Km(1) Arg, Asp, Glu, Leu Val, Leu CL Km(3) Ala, Val 153, 191 G1m(1) 355-358 light chain Allotype Amino Acid Chain Position 153, 191 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 IgG1 (kappa) IgG1 (kappa) Person 1 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 - anti-anti-Id - Immunoglobulin Idiotypes • Definition • Location • Importance – V region marker – Regulation of immune responses – Vaccines Anti-Idiotype Vaccines + Ag Id + anti-Id - Ag Id anti-Id Immunoglobulin Idiotypes • Definition • Location • Importance – – – – V region marker Regulation of immune responses Vaccines Treatment of B cell tumors (T cell) Assignment: As a part of the semester activity, group of students are selected every week to prepare a short seminar about his/her point of interest in one of the lecture topics. That to be discussed and evaluated during the next lecture.