Abstract
A polyamide-based solid-phase support containing an acid-stable p-(oxymethyl)benzoic acid handle to anchor the COOH-terminal amino acid was utilized in the production of synthetic peptides analogous to amino acid sequences 503-532 from the human immunodeficiency virus (HIV) envelope glycoprotein. The resin-bound peptide was used to induce an antibody response to the native form of glycoprotein 120 in both rabbits and mice. This epitope was detected on the surface of HIV-infected cells and was capable of inducing an in vitro neutralizing HIV antibody response. In addition, sera from some individuals exposed to HIV react with this peptide bound to the resin in a solid-phase immunoassay. These data indicate that we have identified a neutralizing antigenic determinant present on the amino-terminal glycoprotein 120 subunits of HIV by utilizing resin-bound synthetic peptides.
Highlights
From the $Department of Virology and ~mmumiogyS,o u t h ~ e s ~ ~ o u n d afotri oBniomedical Research,Sun Antonw, Texas 78284, the TRheumatology and Immumbwlogy Service, Wilford Hall, United States Air Force MedicalCenter, LacklandAir Force Base, Texas 78236, IlDepartment of Cancer Biology, Haruard School of Public Health, Boston, Massachusetts 02115, the **Department of Experimental Medicine, Bayior Coliege of Medicine, Houston, Texas 77030,and the .$.$Infectious Disease UniMt, ~ s a ~ h ~ e t t s General Hospital and Haruard Medical School, Boston,Massachusetts 02115
Evidence is presented to indicate that mouse monoclonal antibodies produced against the resin-bound peptide will stain thecell surface of viable human immunodeficiency virus (HIV)-infected cells, but amino-terminal glycoprotein120 subunits of HIVby utilizing resin-bound synthetic peptides
Our selection of the sequence chosen for preparation of HIV synthetic peptides was based on predictions of a computer program modified by our laboratories [29]
Summary
In this regard, the envelope proteins of murine retroan acid-stablep(oxymethy1)benzoicacid handleto an- viruses have been shown to induce protective immunity (13, chor the COOH-terminal amino acwidas utilized in the 14).The envelope gene product is synthesized as apolyprotein production of synthetic peptides analogous to amino precursor and is subsequently glycosylated within infected acid sequences 503-532 from the human immunode- cells. The etiologic viral agents asso- amino-terminal G P 120-kDa subunit of HIV by utilizing ciated with AIDS have been isolated [4,5,6,7], cloned [8], and resin-bound synthetic peptides This epitope is detectable the nucleotide sequences determined [9,10,11,12]. Agents have been referred to as human T-lymphotropicvirus type I11 (HTLV-111), lymphadenopathy-associated virus
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