Natural auto- and polyreactive antibodies differing from antigen-induced antibodies in the H chain CDR3.
We describe three sets of natural (preimmune) polyreactive antibodies and Ag-induced antibodies that share the same VH-VL combinations. The amino acid homology in the VH and VL segments averaged 92%. These sets were found among 49 neonatal and adult natural mAb that were compared with 35 Ag-induced monoclonals produced during the memory response to phosphocholine (PC)-keyhole limpet hemocyanin. Both groups of monoclonals had been selected on the basis of a restricted fine specificity pattern, namely the ability to recognize PC-protein and p-nitrophenyl phosphocholine but not PC. All of the antibodies were tested for reactivity against a panel of 15 self and foreign Ag. Despite their common fine specificity as the basis for selection, 33/49 natural antibodies were poly/auto reactive whereas 0/35 Ag-induced antibodies had such poly/auto reactive properties. The natural antibodies were encoded by genes representing nine different VH families and several V kappa and V lambda families. There were a few replacement substitutions distinguishing the Ag-induced antibodies from the natural antibodies in each set; however, the most noteworthy difference was the extreme variability of CDR3 in the natural antibodies that differed in both length and amino acid sequence from each other and from Ag-induced antibodies. The results suggest that CDR3 of the H chain may play a critical role in distinguishing poly- from monospecific combining sites in natural and Ag-induced antibodies.
Chen
C
C
Department of Microbiology and Immunology, Oregon Health Sciences University, Portland 97201.
Stenzel-Poore
M P
MP
Rittenberg
M B
MB
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000032:analysis*; D001483:Base Sequence; D005803:Genes, Immunoglobulin; D006825:Hybridomas / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000032:analysis* / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000032:analysis* / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010641:Phenotype
D000906:Antibodies; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region