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Titolo:
ACTIVE IMMUNITY AGAINST THE CD4 RECEPTOR BY USING AN ANTIBODY ANTIGENIZED WITH RESIDUES 41-55 OF THE 1ST EXTRACELLULAR DOMAIN
Autore:
LANZA P; BILLETTA R; ANTONENKO S; ZANETTI M;
Indirizzi:
UNIV CALIF SAN DIEGO,DEPT MED,9500 GILMAN DR LA JOLLA CA 92093 UNIV CALIF SAN DIEGO,DEPT MED,9500 GILMAN DR LA JOLLA CA 92093 UNIV CALIF SAN DIEGO,CTR CANC LA JOLLA CA 92093
Titolo Testata:
Proceedings of the National Academy of Sciences of the United Statesof America
fascicolo: 24, volume: 90, anno: 1993,
pagine: 11683 - 11687
SICI:
0027-8424(1993)90:24<11683:AIATCR>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
IMMUNODEFICIENCY-VIRUS TYPE-1; RECOMBINANT SOLUBLE CD4; INTERCELLULAR-ADHESION MOLECULE-1; HIV-INFECTION; MONOCLONAL-ANTIBODY; SYNCYTIUM FORMATION; DEFICIENCY SYNDROME; RHESUS-MONKEYS; T-CELLS; BINDING;
Keywords:
ANTIGENIZED ANTIBODY; HUMAN IMMUNODEFICIENCY VIRUS; ANTIRECEPTOR IMMUNITY; VACCINATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
46
Recensione:
Indirizzi per estratti:
Citazione:
P. Lanza et al., "ACTIVE IMMUNITY AGAINST THE CD4 RECEPTOR BY USING AN ANTIBODY ANTIGENIZED WITH RESIDUES 41-55 OF THE 1ST EXTRACELLULAR DOMAIN", Proceedings of the National Academy of Sciences of the United Statesof America, 90(24), 1993, pp. 11683-11687

Abstract

Using the process of ''antibody antigenization,'' we engineered two antibody molecules carrying in the third complementarity-determining region of the heavy chain variable domain a 7-mer or a 15-mer peptide epitope of the first extracellular domain (D1) of human CD4 receptor-namely, Ser-Phe-Leu-Thr-Lys-Gly-Pro-Ser (SFLTKGPS; positions 42 through 49) and he-Leu-Thr-Lys-Gly-Pro-Ser-Lys-Leu-Asn-Asp-Arg-Ala (GSFLTKGPSKLNDRA; positions 41 through 55). These amino acid sequences are contained in the consensus binding site for the human immunodeficiency virus (HIV) on CD4 receptor. Both antigenized antibodies ((Ag)Abs) bound recombinant gp120 and were recognized by a prototype monoclonal antibody to CD4 whose binding site is within amino acid residues 41-55. (Ag)Abswere then used as immunogens in rabbits and mice to elicit a humoral response against CD4. Only the (Ag)Ab carrying the sequence 41GSFLTKGPSKLNDRA55 induced a response against CD4. The induced antibodies showed specificity for the amino acid sequence of CD4 engineered in the (Ag)Ab molecule, were able to inhibit the formation of syncytia between human CD4+ T cells MOLT-3 and 8E5 (T cells that are constitutively infected with HIV), and stained human CD4+ CEM T cells. Four murine monoclonal antibodies were used to analyze the relationship between syncytiainhibition and CD4 binding at the single antibody level, and indicated that recognition of native CD4 is not an absolute requirement for inhibition of syncytia. This study demonstrates that antigenized antibodies can be used as immunogens to elicit site-specific and biologicallyactive immunity to CD4. The importance of this approach as a general way to induce anti-receptor immunity and as a possible new measure to immunointervention in HIV infection is discussed.

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Documento generato il 01/12/20 alle ore 10:30:18