Inhibition of normal human natural killer cell activity by human immunodeficiency virus synthetic transmembrane peptides

Abstract

The inhibitory effect on normal natural killer (NK) cell activity of two synthetic peptides corresponding to amino acid sequences 735–752 and 846–860, respectively, as deduced from the amino acid sequences of HTLV-IIIB gp160, was assessed. Sequences 735–752 and 846–860 correspond to regions located within the HIV transmembrane gp41, the carboxy terminus of HIV gp 160. These two synthetic peptides have been shown previously to suppress the mitogenand alloantigen-induced normal human lymphocyte blastogenic responses. Peptides 735–752 and 846–860 conjugated to protein carriers exerted a significant inhibition on the normal NK cell activity assayed against K562 tumor target cells in an in vitro 51Cr-release cytotoxicity assay. At variance, control peptides similarly conjugated had no effect on NK activity. Addition of exogenous recombinant human interleukin-2 (IL-2) resulted in a partial restoration of the suppression of NK cell activity exerted by both peptides. Binding experiments indicated that peptides 735–752 and 846–860 did not affect the formation of effector cell-target cell conjugates, suggesting inhibitory effect(s) subsequent to the formation of the lytic complex as one potential mechanism of the observed NK suppression. These results suggest that peptides 735–752 and 846–860 homologous to sequences within the HIV transmembrane gp41 may play an important role in the pathogenesis of the defective NK cell activity observed in patients with acquired immunodeficiency syndrome (AIDS).