Plasticity within the antigen-combining site may manifest as molecular mimicry in the humoral immune response.
Structural and physiological facets of carbohydrate-peptide mimicry were addressed by analyzing the Ab response to alpha-d-mannopyranoside. mAbs against alpha-d-mannopyranoside were generated and screened with the carbohydrate-mimicking 12 mer (DVFYPYPYASGS) peptide. Three mAbs, 2D10, 1H11, and 1H7, which were subjected to detailed analysis, exhibit diverse V gene usage, indicating their independent germline origins. Although the mAb 1H7 was specific in binding only to the immunizing Ag, the Abs 2D10 and 1H11 recognize the 12 mer peptide as well as the immunogen, alpha-d-mannopyranoside. The Abs that recognize mimicry appear to bind to a common epitope on the peptide and do not share the mode of peptide binding with Con A. Binding kinetics and thermodynamics of Ag recognition suggest that the Ab that does not recognize peptide-carbohydrate mimicry probably has a predesigned mannopyranoside-complementing site. In contrast, the mimicry-recognizing Abs adopt the Ag-combining site only on exposure to the sugar, exploiting the conformational flexibility in the CDRs. Although the mAb 1H7 showed unique specificity toward mannopyranoside, the mimicry-recognizing Abs 2D10 and 1H11 exhibited degenerate specificities with regard to other sugar moieties. It is proposed that the degeneracy of specificity arising from the plasticity at the Ag-combining site in a subset of the Ab clones may be responsible for exhibiting molecular mimicry in the context of Ab response.
Goel
Manisha
M
National Institute of Immunology, New Delhi, India.
Krishnan
Lavanya
L
Kaur
Surinder
S
Kaur
Kanwal J
KJ
Salunke
Dinakar M
DM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000918:Antibody Specificity; D001666:Binding Sites, Antibody; D001667:Binding, Competitive / Q000276:immunology; D022801:Complementarity Determining Regions / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D018604:Epitope Mapping; D005260:Female; D006433:Hemocyanins / Q000276:immunology / Q000378:metabolism; D007135:Immunoglobulin Variable Region / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D008024:Ligands; D008358:Mannose / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018716:Molecular Mimicry / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D017422:Sequence Analysis, DNA; D013816:Thermodynamics
D000911:Antibodies, Monoclonal; D022801:Complementarity Determining Regions; D007135:Immunoglobulin Variable Region; D008024:Ligands; D010446:Peptide Fragments; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin; D008358:Mannose