An idiotype shared by monoclonal antibodies to different peptides of human myelin basic protein.
A mAb of the IgG1/kappa isotype was raised against human myelin basic protein (MBP) peptide acetyl 1-9. This mAb, termed F23, reacted with human MBP and human MBP peptides acetyl 1-9, 1-14, and 1-44, but not with MBP peptides 10-19, 80-89, or 45-89. According to the guidelines of the molecular recognition theory, a complementary peptide to human MBP peptide 1-9 was synthesized and used to raise murine mAb with anti-Id activity. Two mAb anti-Id, F25F7 and F25C8, both of the IgM/kappa isotype, were selected for further study. These anti-Id reacted with F23, the mAb for which they were selected, and also reacted with another mAb, which was of the IgG1/kappa isotype and was raised to human MBP peptide 80-89. There was no reaction with another control mAb of the IgG1/kappa isotype or murine myeloma IgG1. By immunoblotting techniques, it was demonstrated that the Id on each of the mAbs to MBP peptides was located on the kappa L chain but also could be recognized in nonreduced IgG. The cross-reactive anti-Id suppressed antibody secretion of Id-producing hybridoma cells in an Id-specific manner, and kinetic studies suggest an intracellular mechanism for the suppression. These cross-reactive Id among antibodies to different MBP peptides imply that the same V region genes of kappa L chains are involved in the selection of antibodies to an autoantigen, like MBP, and may play a role in the modulation of immune responses against MBP in certain inflammatory demyelinating diseases.
Department of Neurology, University of Alabama, Birmingham.
S R
SR
Zhou
J N
JN
Whitaker
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015153:Blotting, Western; D002417:Cattle; D003429:Cross Reactions; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000276:immunology; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D007145:Immunoglobulin kappa-Chains / Q000276:immunology; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000276:immunology*; D010455:Peptides / Q000276:immunology
D000911:Antibodies, Monoclonal; D007143:Immunoglobulin Heavy Chains; D007130:Immunoglobulin Idiotypes; D007145:Immunoglobulin kappa-Chains; D004676:Myelin Basic Protein; D010455:Peptides