Identical VHD and DJH junctions in monoclonal antibodies derived in response to dextran B512 could be the result of developmental selection.
We describe here the CDR3s of a collection of monoclonal antibodies (MoAb) with specificity for the carbohydrate dextran B512 produced in the mouse strain C57BL/6. In spite of the postulated mechanisms for variability in this region, a high proportion of these monoclonals displayed identical VHD (24/30) and DJH (21/30) junctions and 21 of them were identical in the whole CDR3. These 21 independently generated identical CDR3s could be ordered in eight groups indicating that not a particular CDR3, but instead the mechanism for generating identical junctions was preserved. Two of the CDR3s in this study were found to be identical to the CDR3 of the monoclonal B1-8 produced in C57BL/6 in response to proteins bearing the hapten (4-hydroxy-3-nitrophenyl)acetyl (NP). This and other parameters support the notion that the generation of identical junctions could be independent of antigenic selection. We also report here the association between JH usage and amino acid (aa) residues at the VHD and DJH junctions. Since these MoAb were generated in response to dextran B512, immunoglobulin conformation has to be compatible with antigen binding. Nevertheless, no aa residue of CDR3 could be directly related to antigen binding. We postulate therefore, that the observed selection of CDR3s could be directed to the production of variable regions with protein configuration most suitable with immunoglobulin folding and may occur prior to antigenic selection. Selection for junctional residues in relation to JH usage and the generation of identical CDR3s are probably different events. Possible genetic mechanisms operating for CDR3 construction and/or selection by cellular ligands are discussed.
Fernandez
C
C
Department of Immunology, Wenner-Gren Institute, Stockholm University, Sweden.
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology; D000916:Antibody Diversity / Q000235:genetics* / Q000276:immunology; D001483:Base Sequence; D003911:Dextrans / Q000276:immunology*; D006825:Hybridomas / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data
D000911:Antibodies, Monoclonal; D003911:Dextrans; D007135:Immunoglobulin Variable Region