Are our immunoglobulin V genes pre-adapted for recognizing pathogens: a 3-dimensional analysis (35.53)
| Autor: | Christy Thomson, Steve Bryson, Gary McLean, Emil Pai, John Schrader |
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| Rok vydání: | 2007 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 178:S12-S12 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.178.supp.35.53 |
| Popis: | There is strong phylogenetic evidence that the immunoglobulin V genes that make a major contribution to the generation of diversity of our primary repertoire, are under selective pressure, perhaps by pathogens themselves. Here we report the X-ray crystallographic structural analysis and the consequent kinetic and thermodynamic characteristics of a representative of a subclass of human neutralizing antibodies that originate from a particular pair of Vh and Vk genes and that target a short linear epitope on a human pathogen, HCMV. By comparison of its characteristics with its putative germline ancestors, these studies demonstrate that conserved germline Vh and Vk genes encode key residues in CDR-1 and CDR-2 that are pre-adapted to provide the foundation for the generation of a high-affinity hypermutated antibody. They show that although somatic mutation results in improvements in complimentarity of the binding site, the antibody combining site of the neutralizing antibody does not conform to a lock and key model and retains considerable mobility that is stabilized by interaction with antigen. We speculate that this flexibility may enhance its effectiveness at neutralization of infectivity. |
| Databáze: | OpenAIRE |
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