Octapeptides Deduced from the Neuropeptide Receptor-Like Pattern of Antigen T4 in Brain Potently Inhibit Human Immunodeficiency Virus Receptor Binding and T-Cell Infectivity

• Published in: Proceedings of the National Academy of Sciences - PNAS 1986-12, Vol.83 (23), p.9254-9258
• Main Authors: Pert, Candace B., Hill, Joanna M., Ruff, Michael R., Berman, Robert M., Robey, W. Gerard, Arthur, Larry O., Ruscetti, Francis W., Farrar, William L.
• Format: Article
• Language: English
• Subjects: AIDS; AIDS/HIV; Amides; Amino Acid Sequence; Animals; Antibodies; Antigens; Antigens, Differentiation, T-Lymphocyte; Antigens, Surface - metabolism; Biological and medical sciences; Brain; Brain - metabolism; Cell Differentiation; Cell lines; Cell Membrane - metabolism; Fundamental and applied biological sciences. Psychology; HIV; HIV - metabolism; Humans; Microbiology; Nerve Tissue Proteins - metabolism; Rats; Receptors; Receptors, Virus - metabolism; Saimiri; T lymphocytes; T-Lymphocytes - metabolism; Viral Envelope Proteins - metabolism; Virology; Viruses
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.83.23.9254

The differentiation antigen T4, present on the helper/inducer subset of T lymphocytes, is thought to serve as the receptor for the human immunodeficiency virus (HIV). We find that a 60-kDa protein, immunoprecipitable by monoclonal antibody (mAb) OKT4, is present on membranes from human brain as well as human T cells. Furthermore, the radioiodinated HIV envelope glycoprotein [125I-labeled gp120 (125I-gp120)] can be specifically covalently affixed to a molecule present on rat, monkey, and human brain membranes to yield a complex that is indistinguishable from that formed on human T cells. T4 antigen has been studied on unfixed squirrel monkey, rat, and human brain sections by autoradiography using the mAb OKT4. A highly conserved neuroanatomical pattern has been demonstrated, suggesting an analogous organization in these three mammalian brains. Furthermore, the localization of 125I-gp120 receptor binding appears similar to that of T4 and is highly reminiscent of patterns for many previously characterized neuropeptide receptors. A computer-assisted analysis of gp120 suggested that a previously unremarkable octapeptide sequence within the gp120 protein, which we have synthesized and termed ``peptide T,'' may play an important role in HIV attachment. Thus, peptide T and three rationally designed peptide analogs, each with a systematic amino acid substitution, potently inhibit specific 125I-gp120 binding to brain membranes. Additionally, when tested in a viral infectivity assay, these peptides show the same rank order and similar absolute potency to block HIV infection of human T cells. Thus, peptide T may provide a useful pharmacological or immunological basis for the control and treatment of AIDS.