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Titolo:
ISOLATION OF A NEUTRALIZING HUMAN RSV ANTIBODY FROM A DOMINANT, NONNEUTRALIZING IMMUNE REPERTOIRE BY EPITOPE-BLOCKED PANNING
Autore:
TSUI P; TORNETTA MA; AMES RS; BANKOSKY BC; GRIEGO S; SILVERMAN C; PORTER T; MOORE G; SWEET RW;
Indirizzi:
SMITHKLINE BEECHAM PHARMACEUT,DEPT MOLEC IMMUNOL,UE0548,709 SWEDELANDRD,POB 1539 KING OF PRUSSIA PA 19406 SMITHKLINE BEECHAM PHARMACEUT,DEPT MOL VIROL & HOST DEF KING OF PRUSSIA PA 19406 SMITHKLINE BEECHAM PHARMACEUT,DEPT PROT BIOCHEM KING OF PRUSSIA PA 19406
Titolo Testata:
The Journal of immunology
fascicolo: 2, volume: 157, anno: 1996,
pagine: 772 - 780
SICI:
0022-1767(1996)157:2<772:IOANHR>2.0.ZU;2-D
Fonte:
ISI
Lingua:
ENG
Soggetto:
RESPIRATORY SYNCYTIAL VIRUS; BOVINE MONOCLONAL-ANTIBODIES; F-GLYCOPROTEIN; COMBINATORIAL LIBRARIES; COTTON RATS; INFECTION; INFANTS; IMMUNIZATION; CHILDREN; EXPRESSION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
42
Recensione:
Indirizzi per estratti:
Citazione:
P. Tsui et al., "ISOLATION OF A NEUTRALIZING HUMAN RSV ANTIBODY FROM A DOMINANT, NONNEUTRALIZING IMMUNE REPERTOIRE BY EPITOPE-BLOCKED PANNING", The Journal of immunology, 157(2), 1996, pp. 772-780

Abstract

We isolated a large panel of human Abs directed against the respiratory syncytial virus (RSV) Ag from combinatorial phage display libraries. Following initial differentiation of the Fabs by BstNI restriction patterns, DNA sequence analysis revealed 10 different classes of V-H paired with more than 35 different V-L genes. All the Fabs bound with high affinity to the F Ag. However, most Fabs competed with the binding of a representative member of this group, suggesting that the Fabs recognized a common epitope on the F Ag, and none of them neutralized virus in vitro. To suppress repetitive isolation of these non-neutralizing Abs, a representative Fab was included during panning to block this common epitope on the F Ag. By this ''epitope-blocked panning'' approach, two novel Fabs, encoded by unique V-H and V-L genes, were isolatedfrom a previously screened library. Competition binding analysis confirmed that the Fabs recognized epitopes distinct from that of the previously isolated Fabs. One of these Fabs, 516, neutralized RSV in cell culture. These activities of Fab-516 were retained upon its genetic conversion to a mAb (IgG1) and expression in mammalian cells. Our results suggest that the RSV F glycoprotein presents a dominant, non-neutralizing epitope to the human immune system, which may serve in evasion of host defenses. However, less prevalent, fusion-inhibiting Abs were revealed by blockade of this epitope during the panning process.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 03/07/20 alle ore 01:34:44