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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1986 Dec;83(23):9254–9258. doi: 10.1073/pnas.83.23.9254

Octapeptides deduced from the neuropeptide receptor-like pattern of antigen T4 in brain potently inhibit human immunodeficiency virus receptor binding and T-cell infectivity.

C B Pert, J M Hill, M R Ruff, R M Berman, W G Robey, L O Arthur, F W Ruscetti, W L Farrar
PMCID: PMC387114  PMID: 3097649

Abstract

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.

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Selected References

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