Nature 312, 763 - 767 (20 December 1984); doi:10.1038/312763a0

The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus

Angus G. Dalgleish^*, Peter C. L. Beverley^†, Paul R. Clapham^*, Dorothy H. Crawford^†, Melvyn F. Greaves^* & Robin A. Weiss^*

^*Cell and Molecular Biology Section and LRF Centre, Institute of Cancer Research, Chester Beatty Laboratories, Fulham Road, London SW3 6JB, UK
^†ICRF Human Tumour Immunology Group and Department of Haematology, University College Hospital Medical School, London WC1E 6HX, UK

Acquired immune deficiency syndrome (AIDS) is characterized by opportunistic infections and by 'opportunistic neoplasms' (for example, Kaposi's sarcoma)¹. Persistent generalized lymphadenopathy (PGL) is epidemiologically associated with AIDS, especially in male homosexuals. A subset of T lymphocytes positive for the CD4 antigen² (also termed T4 antigen), is depleted in AIDS and PGL patients. A retrovirus found in T-cell cultures from these patients³⁻⁵ is strongly implicated in the aetiology of AIDS because of the high frequency of isolation⁴ and the prevalence of specific antibodies⁶⁻⁸ in the patients. Here we have detected cell-surface receptors for the AIDS retrovirus (human T-cell leukaemia virus-III (HTLV-III) and lymphadenopathy-associated virus-1 (LAV-1) isolates) by testing the susceptibility of cells to infection with pseudotypes of vesicular stomatitis virus bearing retroviral envelope antigens, and by the formation of multinucleated syncytia on mixing virus-producing cells with receptor-bearing cells. Receptors were present only on cells expressing CD4 antigen; among 155 monoclonal antibodies tested, each of the 14 anti-CD4 antibodies inhibited formation of syncytia and blocked pseudotypes. Productive infection of CD4⁺ cells with HTLV-III or LAV-1 markedly reduced cell-surface expression of CD4. In contrast, receptors for HTLV-I and HTLV-II were not restricted to CD4⁺ cells, were not blocked by anti-CD4 antibodies; cells productively infected with HTLV-I and HTLV-II expressed surface CD4. Hence, we conclude that the CD4 antigen is an essential and specific component of the receptor for the causative agent of AIDS.

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