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Titolo:
Mitogenic properties of a bispecific single-chain Fv-Ig fusion generated from CD2-specific mAb to distinct epitopes
Autore:
Connelly, RJ; Hayden, MS; Scholler, JK; Tsu, TT; Dupont, B; Ledbetter, JA; Kanner, SB;
Indirizzi:
Bristol Myers Squibb Pharmaceut Res Inst, Seattle, WA 98121 USA Bristol Myers Squibb Pharmaceut Res Inst Seattle WA USA 98121 A 98121 USA Mem Sloan Kettering Canc Ctr, Program Immunol, New York, NY 10021 USA Mem Sloan Kettering Canc Ctr New York NY USA 10021 New York, NY 10021 USA
Titolo Testata:
INTERNATIONAL IMMUNOLOGY
fascicolo: 12, volume: 10, anno: 1998,
pagine: 1863 - 1872
SICI:
0953-8178(199812)10:12<1863:MPOABS>2.0.ZU;2-J
Fonte:
ISI
Lingua:
ENG
Soggetto:
T-CELL ACTIVATION; HUMAN LYMPHOCYTES-T; NATURAL-KILLER-CELLS; ALLOANTIGEN-SPECIFIC HYPORESPONSIVENESS; ANTI-CD2 MONOCLONAL-ANTIBODIES; TYROSINE PHOSPHORYLATION; CYTOPLASMIC DOMAIN; ANTIGEN RECEPTOR; CD2 ANTIGEN; SIGNAL TRANSDUCTION;
Keywords:
antibodies; cellular activation; co-stimulatory molecules; signaling; T lymphocytes;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
66
Recensione:
Indirizzi per estratti:
Indirizzo: Kanner, SB Bristol Myers Squibb Pharmaceut Res Inst, POB 4000, Princeton, NJ 08543 USA Bristol Myers Squibb Pharmaceut Res Inst POB 4000 Princeton NJUSA 08543
Citazione:
R.J. Connelly et al., "Mitogenic properties of a bispecific single-chain Fv-Ig fusion generated from CD2-specific mAb to distinct epitopes", INT IMMUNOL, 10(12), 1998, pp. 1863-1872

Abstract

The combination of anti-CDS mAb 9.6 and 9-1, specific for distinct epitopes, induces proliferation of resting human T cells. The mitogenic activity of this mAb mixture depends upon accessory cells and the 9-1 mAb Fc domain. To further study the functional properties of these mAb, their variable regions were cloned and expressed as monospecific single-chain Fv (scFv) proteins fused to the human IgG1 Fc domain (scFvIg). A novel bispecific scFvIg was constructed by cloning the two monospecific scFv binding sites in tandem, with the 9.6 scFv placed N-terminal to the 9-1 scFvIg, Monospecific scFvIg binding to CD2 was comparable to that of the corresponding parental mAb, while the bispecific scFvIg exhibited binding activity similar to that of the 9-1 scFvIg. The combination of 9.6 scFvIg and 9-1 mAb was mitogenic, whereas mixtures including the 9-1 scFvIg were non-stimulatory, confirming theunique properties of the 9-1 IgG3 Fc. Without the IgG3 tail, the bispecific 9.6/9-1 scFvIg was directly mitogenic and was a more potent mitogen than the mAb mixture, but was accessory cell dependent. Unlike the combination of mAb, the bispecific reagent did not directly mobilize calcium in T cells,In comparison to the mAb mixture, bispecific 9.6/9-1 scFvIg-mediated stimulation of a mixed lymphocyte reaction was significantly more resistant to inhibition of the CD28 co-stimulatory pathway by the inhibitor CTLA-4-Ig. These results show that expression of the 9.6 and 9-1 binding sites together on a bispecific scFvIg increased the mitogenic properties of the mAb and altered the degree of accessory cell signals required for T cell activation.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 10/04/20 alle ore 01:30:38