Identification, using synthetic peptides, of the minimum amino acid sequence from the retroviral transmembrane protein p15E required for inhibition of lymphoproliferation and its similarity to gp21 of human T-lymphotropic virus types I and II.
Synthetic peptides containing portions of a highly conserved region of retroviral transmembrane proteins of human and animal retroviruses were tested for their ability to inhibit lymphoproliferation to determine the minimum amino acid sequence required. The previously reported immunosuppression mediated by the peptide CKS-17 was confirmed and further localized to a sequence of eight residues essentially identical to the sequence present in the transmembrane protein gp21 of human T-lymphotropic virus types I and II (HTLV-I and -II). To substantiate the physiological relevance of the inhibition of lymphoproliferation observed with the synthetic peptides and to relate this activity to the intact protein, we purified the Rauscher murine leukemia virus transmembrane protein p15E by immunoaffinity chromatography and report that this purified component presented in the form of protein micelles inhibited the interleukin-2-dependent proliferation of the murine T-cell line CTLL-2 in a dose-dependent manner, with a half-maximal inhibitory dose (ID50) of approximately 16 nM. In comparison, the ID50 concentration of a recombinant form of p15E required to inhibit lymphoproliferation was approximately 2.2 microM. The results reported here support the hypothesis that the transmembrane protein gp21 of HTLV-I and -II participates in the mechanism of immunosuppression previously reported for the transmembrane proteins of feline leukemia virus and other animal retroviruses. Thus, the transmembrane protein of HTLV-I, the etiological agent of adult T-cell leukemia-lymphoma, may be partially responsible for the immunocompromised clinical course of this disease that results in fatal opportunistic infections in a majority of cases.
Ruegg
C L
CL
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Monell
C R
CR
Strand
M
M
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002846:Chromatography, Affinity; D002850:Chromatography, Gel; D004591:Electrophoresis, Polyacrylamide Gel; D015686:Gene Products, env; D015683:Gene Products, gag; D015368:Human T-lymphotropic virus 1 / Q000235:genetics; D015367:Human T-lymphotropic virus 2 / Q000235:genetics; D006801:Humans; D007108:Immune Tolerance; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis; D011925:Rauscher Virus / Q000235:genetics; D012191:Retroviridae Proteins / Q000235:genetics / Q000502:physiology*; D015682:Retroviridae Proteins, Oncogenic; D014759:Viral Envelope Proteins / Q000235:genetics / Q000502:physiology*; D054299:env Gene Products, Human Immunodeficiency Virus
D015686:Gene Products, env; D015683:Gene Products, gag; D010455:Peptides; D012191:Retroviridae Proteins; D015682:Retroviridae Proteins, Oncogenic; D014759:Viral Envelope Proteins; D054299:env Gene Products, Human Immunodeficiency Virus; C055265:gp21 protein, Human T-lymphotropic virus 1; C039467:virus structural protein p15