Immunogenic properties of an anti-DNA antibody-derived peptide, 88H.64-80: location of a dominant idiotope defined by T and B cells.
Immunization of normal (BALB/cxNZW)F1 H-2(dxu) mice with peptide 88H. 64-80 derived from the framework (FR) 3 VH region sequence of anti-DNA mAb, V-88, induces the production of IgG anti-peptide antibodies which cross-react specifically with the parent mAb. However, immunization of these normal mice with peptide 88H.64-80 sometimes provokes increased production of anti-dsDNA antibodies. A set of alanine substitute homologues of peptide 88H.64-80 were made to identify the amino acid residues that contribute to the antigenic status of the peptide. Peptide 88H.64-80 contained an antibody epitope at the carboxyl terminus of the peptide, while substitution of particular residues throughout the peptide had a significant inhibitory effect on T cell stimulation. Finally, subclass analysis of IgG anti-88H.64-80 peptide antibodies revealed a close correlation between the production of IgG2a anti-peptide antibodies (associated with a TH1 T cell response) and the production of IgG anti-dsDNA antibodies, but there was no correlation with any other antibody subclass. Despite the ability of peptide 88H.64-80 to provoke both the production of anti-dsDNA antibodies as well as anti-V region antibodies, the sequence of this peptide differs by only one amino acid residue from a number of murine germline gene-encoded homologues. Peptide 88H.64-80 probably represents an epitope whose appearance correlates with the level of expression of the VH genes that carry its sequence, and as such is characteristic of cross-reactive idiotypes associated with pathology.
Ward
F J
FJ
Infection and Immunity Research Group, King's College London, Campden Hill Road, London, W8 7AH, UK. frank.ward@kcl.ac.uk
Khan
N
N
Wolger
L J
LJ
Howe
C A
CA
Eivazova
E R
ER
Harper
N
N
Muller
S
S
Staines
N A
NA
D000595:Amino Acid Sequence; D000818:Animals; D000974:Antibodies, Antinuclear / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D003429:Cross Reactions; D004247:DNA / Q000737:chemistry / Q000276:immunology; D006801:Humans; D007114:Immunization; D016056:Immunodominant Epitopes / Q000737:chemistry / Q000235:genetics; D007074:Immunoglobulin G / Q000096:biosynthesis; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry / Q000235:genetics; D007130:Immunoglobulin Idiotypes / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D016056:Immunodominant Epitopes; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007130:Immunoglobulin Idiotypes; D010446:Peptide Fragments; D004247:DNA