Abstract
Human T-lymphotropic virus type III (HTLV-III) or lymphadenopathy-associated virus (LAV) is tropic for human T cells with the helper-inducer phenotype, as defined by reactivity with monoclonal antibodies specific for the T4 molecule. Treatment of T4 + T cells with monoclonal antibodies to T4 antigen blocks HTLV-III/LAV binding, syncytia formation, and infectivity. Thus, it has been inferred that the T4 molecule itself is a virus receptor. In the present studies, the surfaces of T4 + T cells were labeled radioactively, and then the cells were exposed to virus. After the cells were lysed, HTLV-III/LAV antibodies were found to precipitate a surface protein with a molecular weight of 58,000 (58K). By blocking and absorption experiments, this 58K protein was identified as the T4 molecule. No cell-surface structures other than the T4 molecule were involved in the antibody-antigen complex formation. Two monoclonal antibodies, each reactive with a separate epitope of the T4 molecule, were tested for their binding capacities in the presence of HTLV-III/LAV. When HTLV-III/LAV was bound to T4 + T cells, the virus blocked the binding of one of the monoclonal antibodies, T4A (OKT4A), but not of the other, T4 (OKT4). When HTLV-III/LAV was internally radiolabeled and bound to T4 + T cells which were then lysed, a viral glycoprotein of 110K (gp110) coprecipitated with the T4 molecule. The binding of gp110 to the T4 molecule may thus be a major factor in HTLV-III/LAV tropism and may prove useful in developing therapeutic or preventive measures for the acquired immune deficiency syndrome.
References
34
Referenced
799
-
ACUTO, O, THE HUMAN T-CELL RECEPTOR - APPEARANCE IN ONTOGENY AND BIOCHEMICAL RELATIONSHIP OF ALPHA-SUBUNITS AND BETA-SUBUNITS ON IL-2 DEPENDENT CLONES AND T-CELL TUMORS, CELL 34: 717 (1983).
(
10.1016/0092-8674(83)90528-7
) / CELL (1983) 10.1126/science.2986290
10.1126/science.2986291
10.1126/science.6189183
-
BREUNER, M.B., CELL 40: 183 (1985).
(
10.1016/0092-8674(85)90321-6
) / CELL (1985) -
BRODER, S, A PATHOGENIC RETROVIRUS (HTLV-III) LINKED TO AIDS, NEW ENGLAND JOURNAL OF MEDICINE 311: 1292 (1984).
(
10.1056/NEJM198411153112006
) / NEW ENGLAND JOURNAL OF MEDICINE (1984) - Clapham, P., Proceedings of the National Academy of Sciences of the United States of America 81: 2886 (1984). / Proceedings of the National Academy of Sciences of the United States of America (1984)
10.1038/312763a0
-
FAUCI, A.S., THE ACQUIRED IMMUNODEFICIENCY SYNDROME - AN UPDATE, ANNALS OF INTERNAL MEDICINE 102: 800 (1985).
(
10.7326/0003-4819-102-6-800
) / ANNALS OF INTERNAL MEDICINE (1985) -
FULLER, T.C., ANTIGENIC POLYMORPHISM OF THE T4 DIFFERENTIATION ANTIGEN EXPRESSED ON HUMAN T-HELPER INDUCER LYMPHOCYTES, HUMAN IMMUNOLOGY 9: 89 (1984).
(
10.1016/0198-8859(84)90031-4
) / HUMAN IMMUNOLOGY (1984) 10.1126/science.6200936
- GOEDERT, J.J., DETERMINANTS OF RETROVIRUS (HTLV-III) ANTIBODY AND IMMUNODEFICIENCY CONDITIONS IN HOMOSEXUAL MEN, LANCET 2: 711 (1984). / LANCET (1984)
10.1038/312767a0
10.1126/science.6328660
-
LANE, H.C., QUALITATIVE-ANALYSIS OF IMMUNE FUNCTION IN PATIENTS WITH THE ACQUIRED IMMUNODEFICIENCY SYNDROME - EVIDENCE FOR A SELECTIVE DEFECT IN SOLUBLE-ANTIGEN RECOGNITION, NEW ENGLAND JOURNAL OF MEDICINE 313: 79 (1985).
(
10.1056/NEJM198507113130204
) / NEW ENGLAND JOURNAL OF MEDICINE (1985) -
LAURENCE, J, LYMPHADENOPATHY-ASSOCIATED VIRAL ANTIBODY IN AIDS - IMMUNE CORRELATIONS AND DEFINITION OF A CARRIER STATE, NEW ENGLAND JOURNAL OF MEDICINE 311: 1269 (1984).
(
10.1056/NEJM198411153112001
) / NEW ENGLAND JOURNAL OF MEDICINE (1984) -
MCDOUGAL, J.S., CELLULAR TROPISM OF THE HUMAN RETROVIRUS HTLV-III/LAV .1. ROLE OF T-CELL ACTIVATION AND EXPRESSION OF THE T4 ANTIGEN, JOURNAL OF IMMUNOLOGY 135: 3151 (1985).
(
10.4049/jimmunol.135.5.3151
) / JOURNAL OF IMMUNOLOGY (1985) -
MCDOUGAL, J.S., IMMUNOASSAY FOR THE DETECTION AND QUANTITATION OF INFECTIOUS HUMAN RETROVIRUS, LYMPHADENOPATHY-ASSOCIATED VIRUS (LAV), JOURNAL OF IMMUNOLOGICAL METHODS 76: 171 (1985).
(
10.1016/0022-1759(85)90489-2
) / JOURNAL OF IMMUNOLOGICAL METHODS (1985) -
NARAYAN, O, NEUTRALIZING ANTIBODY SPECTRUM DETERMINES THE ANTIGENIC PROFILES OF EMERGING MUTANTS OF VISNA VIRUS, INFECTION AND IMMUNITY 32: 1045 (1981).
(
10.1128/iai.32.3.1045-1050.1981
) / INFECTION AND IMMUNITY (1981) -
NEVILLE, D.M., METHODS IN ENZYMOLOGY 32: 92 (1974).
(
10.1016/0076-6879(74)32012-5
) / METHODS IN ENZYMOLOGY (1974) -
NICHOLSON, JKA, EXPOSURE TO HUMAN T-LYMPHOTROPIC VIRUS TYPE-III LYMPHADENOPATHY-ASSOCIATED VIRUS AND IMMUNOLOGICAL ABNORMALITIES IN ASYMPTOMATIC HOMOSEXUAL MEN, ANNALS OF INTERNAL MEDICINE 103: 37 (1985).
(
10.7326/0003-4819-103-1-37
) / ANNALS OF INTERNAL MEDICINE (1985) - POPOVIC, M, T4 POSITIVE HUMAN NEOPLASTIC CELL-LINES SUSCEPTIBLE TO AND PERMISSIVE FOR HTLV-III, LANCET 2: 1472 (1984). / LANCET (1984)
10.1126/science.6200935
-
PORATH, J, CHEMICAL COUPLING OF PROTEINS TO AGAROSE, NATURE 215: 1491 (1967).
(
10.1038/2151491a0
) / NATURE (1967) 10.1038/313277a0
-
ROBERTGUROFF, M, HTLV-III-NEUTRALIZING ANTIBODIES IN PATIENTS WITH AIDS AND AIDS-RELATED COMPLEX, NATURE 316: 72 (1985).
(
10.1038/316072a0
) / NATURE (1985) 10.1126/science.6324345
10.1126/science.6200937
10.1126/science.6095449
10.1126/science.6967228
10.1126/science.2994223
-
WEISS, R.A., NEUTRALIZATION OF HUMAN T-LYMPHOTROPIC VIRUS TYPE-III BY SERA OF AIDS AND AIDS-RISK PATIENTS, NATURE 316: 69 (1985).
(
10.1038/316069a0
) / NATURE (1985) 10.1126/science.2992084
-
ZAVADA, J, PSEUDOTYPES OF VESICULAR STOMATITIS-VIRUS WITH COAT OF MURINE LEUKEMIA AND OF AVIAN MYELOBLASTOSIS VIRUSES, JOURNAL OF GENERAL VIROLOGY 15: 183 (1972).
(
10.1099/0022-1317-15-3-183
) / JOURNAL OF GENERAL VIROLOGY (1972)
Dates
Type | When |
---|---|
Created | 18 years, 10 months ago (Oct. 5, 2006, 4:28 p.m.) |
Deposited | 1 year, 7 months ago (Jan. 13, 2024, 10:17 a.m.) |
Indexed | 4 months ago (April 18, 2025, 11:24 a.m.) |
Issued | 39 years, 6 months ago (Jan. 24, 1986) |
Published | 39 years, 6 months ago (Jan. 24, 1986) |
Published Print | 39 years, 6 months ago (Jan. 24, 1986) |
@article{McDougal_1986, title={Binding of HTLV-III/LAV to T4 + T Cells by a Complex of the 110K Viral Protein and the T4 Molecule}, volume={231}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.3001934}, DOI={10.1126/science.3001934}, number={4736}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={McDougal, J. S. and Kennedy, M. S. and Sligh, J. M. and Cort, S. P. and Mawle, A. and Nicholson, J. K. A.}, year={1986}, month=jan, pages={382–385} }