Faculty Collaboration Database

Polyvalent human immunodeficiency virus synthetic immunogen comprised of envelope gp120 T helper cell sites and B cell neutralization epitopes. J Immunol 1989 May 15;142(10):3612-9

Date

05/15/1989

Pubmed ID

2469721

Scopus ID

2-s2.0-0024382144 (requires institutional sign-in at Scopus site)   136 Citations

Abstract

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.

Author List

Palker TJ, Matthews TJ, Langlois A, Tanner ME, Martin ME, Scearce RM, Kim JE, Berzofsky JA, Bolognesi DP, Haynes BF

MESH terms used to index this publication - Major topics in bold

Amino Acid Sequence
Animals
Antibodies, Viral
Antigens, Viral
B-Lymphocytes
Epitopes
Goats
HIV
HIV Envelope Protein gp120
Immune Sera
Immunologic Memory
Lymphocyte Activation
Mice
Molecular Sequence Data
Neutralization Tests
Peptide Fragments
Recombinant Proteins
Retroviridae Proteins
T-Lymphocytes, Helper-Inducer