Construction of peptides encompassing multideterminant clusters of human immunodeficiency virus envelope to induce in vitro T cell responses in mice and humans of multiple MHC types
J A Berzofsky, C D Pendleton, M Clerici, J Ahlers, D R Lucey, S D Putney, G M Shearer, J A Berzofsky, C D Pendleton, M Clerici, J Ahlers, D R Lucey, S D Putney, G M Shearer
Abstract
To make synthetic peptide vaccines effective in a broad population of outbred humans, one would have to incorporate enough antigenic determinants to elicit recognition by T cells of most HLA types. We have previously defined multideterminant regions of the human immunodeficiency virus (HIV) envelope that include overlapping determinants seen by proliferating T cells of three or four haplotypes of mice. We have now tested the hypothesis that synthetic peptides encompassing such multideterminant regions will be recognized by T cells of multiple murine MHC types as well as by human T cells representing multiple HLA types. Six such peptides of 20-33 residues in length were prepared, and tested for their ability to stimulate T cells from mice of four distinct MHC types immunized with recombinant envelope protein rgp 160, as well as from 42 HIV-infected humans of different HLA types. Results identify several such peptides that are broadly recognized by mice of four H-2 types and by 52-73% of infected humans who still retain IL-2 productive responses to control recall antigens such as influenza A virus or tetanus toxoid. 86% of such infected donors tested against at least three peptides respond to at least one of the six peptides, and 77% of an additional group of seropositives respond to a mixture of the peptides. Moreover, the peptides can be used to immunize mice to elicit T cells reactive with the intact HIV envelope protein. These peptides therefore may be useful for both vaccine development in the broad human population, and diagnostic or prognostic use.
References
- Int Immunol. 1989;1(4):409-15
- J Infect Dis. 1991 Jul;164(1):178-82
- J Exp Med. 1989 Dec 1;170(6):2023-35
- J Clin Invest. 1989 Dec;84(6):1892-9
- Science. 1989 Oct 6;246(4926):118-21
- Nature. 1988 Aug 25;334(6184):706-8
- Nature. 1989 Jun 1;339(6223):383-5
- Science. 1988 Oct 28;242(4878):580-3
- J Clin Invest. 1988 Dec;82(6):1811-7
- Cell. 1988 Aug 12;54(4):561-75
- Immunol Rev. 1988 Dec;106:5-31
- Methods Enzymol. 1989;178:611-34
- Eur J Immunol. 1989 Dec;19(12):2237-42
- J Immunol. 1989 Nov 1;143(9):2814-9
- J Immunol. 1989 Aug 1;143(3):771-9
- J Immunol. 1989 May 1;142(9):3091-7
- Mol Biol Med. 1988 Dec;5(3):185-96
- J Clin Invest. 1989 Apr;83(4):1430-5
- J Exp Med. 1990 Feb 1;171(2):571-6
- J Immunol. 1990 Jul 15;145(2):540-8
- Proc Natl Acad Sci U S A. 1990 Mar;87(6):2344-8
- J Immunol. 1990 May 1;144(9):3341-6
- Proc Natl Acad Sci U S A. 1990 Apr;87(8):3185-9
- Nature. 1982 Nov 4;300(5887):66-9
- J Immunol. 1983 Apr;130(4):1527-35
- J Immunol. 1977 Sep;119(3):1048-53
- J Immunol. 1978 Jun;120(6):1809-12
- J Exp Med. 1988 Jul 1;168(1):357-73
- Nature. 1988 Dec 22-29;336(6201):778-80
- Proc Natl Acad Sci U S A. 1988 May;85(9):3105-9
- Proc Natl Acad Sci U S A. 1988 Feb;85(4):1199-203
- Immunol Rev. 1987 Aug;98:53-73
- Proc Natl Acad Sci U S A. 1987 Jun;84(12):4249-53
- J Immunol. 1987 Apr 1;138(7):2213-29
- Science. 1987 Feb 20;235(4791):865-70
- Science. 1987 Feb 27;235(4792):1059-62
- J Immunol. 1987 Jan 1;138(1):204-12
- N Engl J Med. 1985 Jul 11;313(2):79-84
- Proc Natl Acad Sci U S A. 1985 Oct;82(20):7048-52
- Annu Rev Immunol. 1985;3:237-61
- Nature. 1985 Jan 24-30;313(6000):277-84
- Science. 1989 Sep 22;245(4924):1380-2
- Nature. 1989 Nov 30;342(6249):561-4
- J Immunol. 1989 Feb 15;142(4):1166-76
- Proc Natl Acad Sci U S A. 1989 Sep;86(17):6768-72
- Science. 1988 Jan 29;239(4839):476-81
- J Immunol. 1984 Dec;133(6):3371-7
- J Exp Med. 1986 Apr 1;163(4):903-21
- Nature. 1986 Aug 21-27;322(6081):687-9
- Nature. 1990 Apr 26;344(6269):873-5
- J Immunol. 1990 Nov 1;145(9):2880-5
- J Exp Med. 1991 Jan 1;173(1):19-24
- Proc Natl Acad Sci U S A. 1989 Jun;86(12):4710-4
Source: PubMed