Synthetic peptides homologous to HIV transmembrane glycoprotein suppress normal human lymphocyte blastogenic response.
Human immunodeficiency virus (HIV) envelope glycoprotein is synthesized as a polyprotein precursor of 160 kDa (gp 160) and is subsequently cleaved into an amino terminus subunit, gp 120, and a carboxyl terminus transmembrane subunit, gp 41. Two synthetic peptides corresponding to amino acid sequences 735-752 and 846-860, respectively, as deduced from the nucleotide sequence of HTLV-IIIB gp 160 were synthesized and used to assess their effects on normal human lymphocyte blastogenesis. Peptides 735-752 and 846-860 conjugated to protein carriers, but not free peptides, exerted a pronounced suppression of the normal human lymphocyte proliferative response to concanavalin A (Con A), phytohemagglutinin (PHA), pokeweed mitogen (PWM), and alloantigens. A synthetic peptide homologous to a 17 amino acid sequence of the gene product of HIV trans-acting transcriptional (TAT III) gene had no suppressive effects. Peptides 735-752 and 846-860 also inhibited the IL-2-dependent proliferation of the murine CTLL-2 cell line and the PHA-induced proliferation of normal mouse spleen cells. HIV peptide-induced suppression of human blastogenesis required a 2- to 3-day incubation of responder cells with peptides, suggesting that binding of peptides to the cell membrane was not sufficient for suppression. These results suggest that, in addition to the selective cytopathic effects of HIV, the etiological agent of the acquired immunodeficiency syndrome (AIDS), on the T-helper/inducer lymphocyte subset, viral peptide-mediated immunosuppression may also play an important role in the pathogenesis of the disease. Moreover, these data clearly indicate the need to address the potential immunosuppressive property of HIV antigens in the effort to select and develop effective prophylactic means against AIDS.
Chanh
T C
TC
Department of Virology and Immunology, Southwest Foundation for Biomedical Research, San Antonio, Texas 78284.
Kennedy
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RC
Kanda
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P
D006023:Glycoproteins / Q000276:immunology*; D006678:HIV / Q000276:immunology*; D007108:Immune Tolerance; D007376:Interleukin-2 / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D014759:Viral Envelope Proteins / Q000276:immunology*
D006023:Glycoproteins; D007376:Interleukin-2; D010455:Peptides; D014759:Viral Envelope Proteins