Natural mouse and human antibodies bind to a peptide derived from a germline VH chain. Evidence for evolutionary conserved self-binding locus.
Murine antibodies derived from the V1 S107/T15 germline structure combined with Vk 22 L chains express the property of self-binding. Previous studies have shown that the self-binding is mediated by the Fab fragment involving structures of the hapten binding site. The molecular locus of self-binding has also been identified by showing that a peptide derived from the CDR2/FR3 region of the V1 S107 H chain inhibits self-binding. We have addressed the question of whether self-binding antibodies interact with peptides that inhibit self-binding. We found that labeled TEPC15 (T15) binds to immobilized VH (50-73) peptide; the peptide binding is specific because different CDR peptides and other unrelated peptides do not inhibit this binding. Furthermore, the hapten phosphorylcholine is a potent inhibitor for the T15-peptide binding. We have demonstrated the presence of naturally occurring antibodies that bind to the T15H(50-73) peptide in the sera of different strains of mice and also in humans, indicating that the CDR2/FR3 sequence of T15 is a conserved Id determining region. We have isolated peptide-specific antibodies from pooled normal human Ig preparations. Human anti-peptide antibodies have self-binding properties similar to their murine counterparts. This interspecies conserved peptide binding of antibodies that are self-binding indicates the existence of an evolutionarily important and biologically active site.
Kaveri
S V
SV
IDEC Pharmaceuticals Corporation, La Jolla, CA 92037.
Kang
C Y
CY
Köhler
H
H
D000818:Animals; D000906:Antibodies / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005075:Biological Evolution; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000378:metabolism*; D007130:Immunoglobulin Idiotypes; D007135:Immunoglobulin Variable Region / Q000378:metabolism*; D066298:In Vitro Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000276:immunology*; D011485:Protein Binding
D000906:Antibodies; D007143:Immunoglobulin Heavy Chains; D007130:Immunoglobulin Idiotypes; D007135:Immunoglobulin Variable Region; D010455:Peptides