Germline V-genes sculpt the binding site of a family of antibodies neutralizing human cytomegalovirus.
EMBO J
; 27(19): 2592-602, 2008 Oct 08.
Article
em En
| MEDLINE
| ID: mdl-18772881
ABSTRACT
Immunoglobulin genes are generated somatically through specialized mechanisms resulting in a vast repertoire of antigen-binding sites. Despite the stochastic nature of these processes, the V-genes that encode most of the antigen-combining site are under positive evolutionary selection, raising the possibility that V-genes have been selected to encode key structural features of binding sites of protective antibodies against certain pathogens. Human, neutralizing antibodies to human cytomegalovirus that bind the AD-2S1 epitope on its gB envelope protein repeatedly use a pair of well-conserved, germline V-genes IGHV3-30 and IGKV3-11. Here, we present crystallographic, kinetic and thermodynamic analyses of the binding site of such an antibody and that of its primary immunoglobulin ancestor. These show that these germline V-genes encode key side chain contacts with the viral antigen and thereby dictate key structural features of the hypermutated, high-affinity neutralizing antibody. V-genes may thus encode an innate, protective immunological memory that targets vulnerable, invariant sites on multiple pathogens.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Sítios de Ligação de Anticorpos
/
Região Variável de Imunoglobulina
/
Genes de Imunoglobulinas
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Citomegalovirus
/
Anticorpos Monoclonais
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
EMBO J
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Canadá