PMID- 2469721 OWN - NLM STAT- MEDLINE DCOM- 19890619 LR - 20071114 IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 142 IP - 10 DP - 1989 May 15 TI - Polyvalent human immunodeficiency virus synthetic immunogen comprised of envelope gp120 T helper cell sites and B cell neutralization epitopes. PG - 3612-9 AB - In previous studies, we have used antisera raised to envelope (env)-gene-encoded synthetic peptides to identify a region of (HIV) glycoprotein (gp) 120 env protein designated SP10 that contains a type-specific neutralizing determinant. To develop a polyvalent, synthetic peptide inoculum that can evoke both neutralizing antibodies and T cell proliferative responses to more than one HIV isolate, synthetic peptides containing type-specific neutralizing determinants of gp120 from HIV isolates HTLV-IIIB (IIIB), HTLV-IIIMN (MN) and HTLV-IIIRF (RF) were coupled to a 16 amino acid T cell epitope (T1) of HIV-IIIB gp120 and used to immunize goats. Goat antisera to each T1-SP10 peptide derived from the SP10 region of gp120 of IIIB, MN, and RF neutralized HIV isolates IIIB, MN and RF in a type-specific manner. Moreover, peripheral blood T cells from immunized goats also proliferated in a type-specific manner to peptides derived from gp120 of IIIB, MN, and RF. When combined in a trivalent inoculum, T1-SP10 peptides from HIV-1 isolates IIIB, MN, and RF evoked a high titered neutralizing antibody response to isolates IIIB, MN, and RF in goats and as well induced immune T cells to undergo blast transformation in the presence of peptides derived from gp120 of all three HIV isolates. The T1 portion of the T1-SP10 construct was shown to induce a B cell antibody response against determinants within the T1 peptide in addition to inducing T cell proliferative responses in immune goat T cells. Moreover, the SP10 portion of the T1-SP10 constructs not only induced B cell antibody production but also induced type-specific T cell proliferative responses localized to the C-terminal variable sequences of the SP10 peptides. Finally, the T1-SP10 peptide construct induced memory T cell proliferative responses to native gp120 env protein. Thus, combinations of homologous SP10 region synthetic peptides containing type-specific neutralizing determinants and T cell epitopes of HIV gp120 may be useful in man to elicit high titered neutralizing B cell responses and, as well, T cell responses to more than one HIV isolate. FAU - Palker, T J AU - Palker TJ AD - Department of Medicine, Duke University Medical Center, Durham, NC 27710. FAU - Matthews, T J AU - Matthews TJ FAU - Langlois, A AU - Langlois A FAU - Tanner, M E AU - Tanner ME FAU - Martin, M E AU - Martin ME FAU - Scearce, R M AU - Scearce RM FAU - Kim, J E AU - Kim JE FAU - Berzofsky, J A AU - Berzofsky JA FAU - Bolognesi, D P AU - Bolognesi DP FAU - Haynes, B F AU - Haynes BF LA - eng GR - P01 CA43447/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Antibodies, Viral) RN - 0 (Antigens, Viral) RN - 0 (Epitopes) RN - 0 (HIV Envelope Protein gp120) RN - 0 (Immune Sera) RN - 0 (Peptide Fragments) RN - 0 (Recombinant Proteins) RN - 0 (Retroviridae Proteins) SB - IM MH - Amino Acid Sequence MH - Animals MH - Antibodies, Viral/biosynthesis MH - Antigens, Viral/analysis/*immunology MH - B-Lymphocytes/*immunology/metabolism MH - Epitopes/analysis/immunology MH - Goats MH - HIV/*immunology/isolation & purification MH - HIV Envelope Protein gp120 MH - Immune Sera MH - Immunologic Memory MH - Lymphocyte Activation MH - Mice MH - Molecular Sequence Data MH - Neutralization Tests MH - Peptide Fragments/chemical synthesis/immunology MH - Recombinant Proteins/analysis/*immunology MH - Retroviridae Proteins/analysis/*immunology MH - T-Lymphocytes, Helper-Inducer/*immunology EDAT- 1989/05/15 00:00 MHDA- 1989/05/15 00:01 CRDT- 1989/05/15 00:00 PHST- 1989/05/15 00:00 [pubmed] PHST- 1989/05/15 00:01 [medline] PHST- 1989/05/15 00:00 [entrez] PST - ppublish SO - J Immunol. 1989 May 15;142(10):3612-9.