The fusogenic (F) domain of human immunodeficiency virus (HIV) gp41 envelope (env) protein has sequence similarities to many virus and mediates the fusion of HIV-infected cells. During a survey of the immunogenicity of HIV env peptides in chimpanzees, we have observed that HIV peptide immunogenicity was dramatically altered by the NH2-terminal synthesis of the gp41 F domain to an otherwise immunogenic peptide. We compared two hybrid peptide types comprised of T helper (Th) and B cell epitopes of HIV gp120 env protein for their immunogenicity in chimpanzees. The Th-B epitope hybrid peptides contained the HIV gp120 Th cell determinant, T1 (amino acids [aa] 428-440)-synthesized NH2 terminal to gp120 V3 loop peptides, which contain B cell epitopes that induce anti-HIV-neutralizing antibodies (SP10IIIB [aa 303-321] and SP10IIIB [A] [aa 303-327]). The F-Th-B peptide contained the HIV gp41 F domain of HIVIIIB gp41 (aa 519-530)-synthesized NH2 terminal to the Th-B peptide. Whereas Th-B peptides were potent immunogens for chimpanzee antibody and T cell-proliferative responses, the F-Th-B peptide induced lower anti-HIV gp120 T and B cell responses. Moreover, immunization of chimpanzees with F-Th-B peptide but not Th-B peptides induced a significant decrease in peripheral blood T lymphocytes (mean decrease during immunization, 52%; p < 0.02). Chimpanzees previously immunized with F-Th-B peptide did not respond well to immunization with Th-B peptide with T or B cell responses to HIV peptides, demonstrating that the F-Th-B peptide induced immune hyporesponsiveness to Th and B HIV gp120 env determinants. These observations raise the hypothesis that the HIV gp41 env F domain may be a biologically active immunoregulatory peptide in vivo, and by an as yet uncharacterized mechanism, promotes primate immune system hyporesponsiveness to otherwise immunogenic peptides.
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1 March 1993
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March 01 1993
Conversion of an immunogenic human immunodeficiency virus (HIV) envelope synthetic peptide to a tolerogen in chimpanzees by the fusogenic domain of HIV gp41 envelope protein.
B F Haynes,
B F Haynes
Department of Medicine, Duke Center for AIDS Research, Duke University Medical Center, Durham, North Carolina 27710.
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L O Arthur,
L O Arthur
Department of Medicine, Duke Center for AIDS Research, Duke University Medical Center, Durham, North Carolina 27710.
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P Frost,
P Frost
Department of Medicine, Duke Center for AIDS Research, Duke University Medical Center, Durham, North Carolina 27710.
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T J Matthews,
T J Matthews
Department of Medicine, Duke Center for AIDS Research, Duke University Medical Center, Durham, North Carolina 27710.
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A J Langlois,
A J Langlois
Department of Medicine, Duke Center for AIDS Research, Duke University Medical Center, Durham, North Carolina 27710.
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T J Palker,
T J Palker
Department of Medicine, Duke Center for AIDS Research, Duke University Medical Center, Durham, North Carolina 27710.
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M K Hart,
M K Hart
Department of Medicine, Duke Center for AIDS Research, Duke University Medical Center, Durham, North Carolina 27710.
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R M Scearce,
R M Scearce
Department of Medicine, Duke Center for AIDS Research, Duke University Medical Center, Durham, North Carolina 27710.
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D M Jones,
D M Jones
Department of Medicine, Duke Center for AIDS Research, Duke University Medical Center, Durham, North Carolina 27710.
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C McDanal
C McDanal
Department of Medicine, Duke Center for AIDS Research, Duke University Medical Center, Durham, North Carolina 27710.
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B F Haynes
Department of Medicine, Duke Center for AIDS Research, Duke University Medical Center, Durham, North Carolina 27710.
L O Arthur
Department of Medicine, Duke Center for AIDS Research, Duke University Medical Center, Durham, North Carolina 27710.
P Frost
Department of Medicine, Duke Center for AIDS Research, Duke University Medical Center, Durham, North Carolina 27710.
T J Matthews
Department of Medicine, Duke Center for AIDS Research, Duke University Medical Center, Durham, North Carolina 27710.
A J Langlois
Department of Medicine, Duke Center for AIDS Research, Duke University Medical Center, Durham, North Carolina 27710.
T J Palker
Department of Medicine, Duke Center for AIDS Research, Duke University Medical Center, Durham, North Carolina 27710.
M K Hart
Department of Medicine, Duke Center for AIDS Research, Duke University Medical Center, Durham, North Carolina 27710.
R M Scearce
Department of Medicine, Duke Center for AIDS Research, Duke University Medical Center, Durham, North Carolina 27710.
D M Jones
Department of Medicine, Duke Center for AIDS Research, Duke University Medical Center, Durham, North Carolina 27710.
C McDanal
Department of Medicine, Duke Center for AIDS Research, Duke University Medical Center, Durham, North Carolina 27710.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1993) 177 (3): 717–727.
Citation
B F Haynes, L O Arthur, P Frost, T J Matthews, A J Langlois, T J Palker, M K Hart, R M Scearce, D M Jones, C McDanal; Conversion of an immunogenic human immunodeficiency virus (HIV) envelope synthetic peptide to a tolerogen in chimpanzees by the fusogenic domain of HIV gp41 envelope protein.. J Exp Med 1 March 1993; 177 (3): 717–727. doi: https://doi.org/10.1084/jem.177.3.717
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