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.
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.
Berzofsky
J A
JA
Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Pendleton
C D
CD
Clerici
M
M
Ahlers
J
J
Lucey
D R
DR
Putney
S D
SD
Shearer
G M
GM
D000818:Animals; D001483:Base Sequence; D000939:Epitopes / Q000032:analysis*; D015686:Gene Products, env / Q000276:immunology*; D006183:H-2 Antigens / Q000032:analysis*; D006678:HIV / Q000276:immunology*; D019302:HIV Envelope Protein gp160; D015658:HIV Infections / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000032:analysis*; D000949:Histocompatibility Antigens Class II / Q000032:analysis*; D006801:Humans; D007114:Immunization; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology*; D011498:Protein Precursors / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology
D000939:Epitopes; D015686:Gene Products, env; D006183:H-2 Antigens; D019302:HIV Envelope Protein gp160; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D010446:Peptide Fragments; D011498:Protein Precursors; D014614:Vaccines, Synthetic; D014765:Viral Vaccines