Diversity in the CDR3 region of V(H) is sufficient for most antibody specificities.
All rearranging antigen receptor genes have one or two highly diverse complementarity determining regions (CDRs) among the six that typically form the ligand binding surface. We report here that, in the case of antibodies, diversity at one of these regions, CDR3 of the V(H) domain, is sufficient to permit otherwise identical IgM molecules to distinguish between a variety of hapten and protein antigens. Furthermore, we find that somatic mutation can allow such antibodies to achieve surprisingly high affinities. These results are consistent with a model in which the highly diverse CDR3 loops are the key determinant of specificity in antigen recognition in both T cell receptors (TCR) and antibodies, whereas the germline-encoded CDR1 and CDR2 sequences are much more cross-reactive.
Department of Microbiology and Immunology, Stanford University School of Medicine, California 94305, USA.
J L
JL
Xu
M M
MM
Davis
D000595:Amino Acid Sequence; D000818:Animals; D000915:Antibody Affinity; D000916:Antibody Diversity / Q000276:immunology*; D000918:Antibody Specificity / Q000276:immunology*; D000941:Antigens / Q000276:immunology; D022801:Complementarity Determining Regions; D003911:Dextrans / Q000276:immunology; D006241:Haptens / Q000276:immunology; D006433:Hemocyanins / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry / Q000276:immunology*; D007075:Immunoglobulin M / Q000737:chemistry / Q000276:immunology*; D007135:Immunoglobulin Variable Region / Q000276:immunology*; D007145:Immunoglobulin kappa-Chains / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010047:Ovalbumin / Q000276:immunology; D011135:Polysaccharides, Bacterial / Q000276:immunology; D017421:Sequence Analysis
C042158:2,4-dinitrophenyl keyhole limpet hemocyanin; D000941:Antigens; D022801:Complementarity Determining Regions; D003911:Dextrans; D006241:Haptens; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D011135:Polysaccharides, Bacterial; D010047:Ovalbumin; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin