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Titolo:
MOLECULAR-SELECTION OF HUMAN-ANTIBODIES WITH AN UNCONVENTIONAL BACTERIAL B-CELL ANTIGEN
Autore:
SASANO M; BURTON DR; SILVERMAN GJ;
Indirizzi:
UNIV CALIF SAN DIEGO,DEPT MED 0663,THEODORE GILDRED CANC CTR,9500 GILMAN DR LA JOLLA CA 92093 UNIV CALIF SAN DIEGO,DEPT MED 0663,THEODORE GILDRED CANC CTR,9500 GILMAN DR LA JOLLA CA 92093 UNIV CALIF SAN DIEGO,SAM & ROSE STEIN INST RES AGING LA JOLLA CA 92093 SCRIPPS CLIN & RES INST LA JOLLA CA 92037
Titolo Testata:
The Journal of immunology
fascicolo: 10, volume: 151, anno: 1993,
pagine: 5822 - 5839
SICI:
0022-1767(1993)151:10<5822:MOHWAU>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
STAPHYLOCOCCAL PROTEIN-A; HUMAN MONOCLONAL-ANTIBODIES; VARIABLE REGION GENES; VH GENE; T-CELLS; H-CHAIN; SOMATIC MUTATION; ENTEROTOXIN-B; FAB FRAGMENTS; HUMAN-IGM;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
78
Recensione:
Indirizzi per estratti:
Citazione:
M. Sasano et al., "MOLECULAR-SELECTION OF HUMAN-ANTIBODIES WITH AN UNCONVENTIONAL BACTERIAL B-CELL ANTIGEN", The Journal of immunology, 151(10), 1993, pp. 5822-5839

Abstract

Unconventional Ag for B cells that are comparable to known superantigens for T lymphocytes have not been well characterized. However, the bacterial membrane protein, Staphylococcal protein A (SpA), has sites that interact with the Fab of many IgM, IgA, IgG, and IgE, and in recent reports we have provided evidence of V(H) restriction in Fab that bind SpA. To investigate the molecular basis for this Fab binding specificity, we have selected monoclonal Fab from a phage-display combinatorial Ig library, based on the ability to bind SpA. By this approach, inan unselected human polyclonal IgG Fab library, about 17% of antibody-expressing clones were found to bind SpA. SpA binding was completely restricted to Fab with V(H)3 H chains, and about 60% of V(H)3 Fab in the unselected library had SpA binding capacity. Analysis of 21 V(H) sequences and 6 V(L) sequences demonstrated that Fab that bind SpA use diverse V(H)3 genes, while the L chains derive from a variety of V(kappa) and V(lambda) gene families. By creation of antibodies with differential H-L chain pairing, the global capacity to bind SpA was shown to be dictated by V(H)3 usage, but different L chain usage could result in up to a fourfold change in binding affinity. The apparent K(D) of the SpA binding by different Fab ranged from 2.5 x 10(-7) to >10(-5) M. Furthermore, repeated rounds of in vitro panning selected for antibodies based on higher binding affinity. These data indicate that the pattern of V(H) family restriction of Ig reactive with SpA is comparable to known superantigens, and there is a hierarchy within the binding affinities of V(H)3 Fab based on V gene usage.

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Documento generato il 23/09/20 alle ore 15:23:55