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.
The virus that causes the acquired immunodeficiency syndrome (AIDS), human T lymphotropic virus/lymphadenopathy-associated virus (HTLV-III/LAV), was incubated at temperatures from 370 to 60'C and virus titer
In defining the relation ofT-cell sets to one another, the prime task is to determine, for a given pair of cell sets jointly required for a particular function, whether one set is recruited from the other by differentiation (developmental sequence) or whether the relationship is entirely communicative (collaboration or induction).The cell sets Ly123 and Lyl are a case in point. From indirect evidence it has been inferred that Ly123 is the precursor set for Lyl cells that act as helper-effectors (HE) x (Ly 1 :HE cells) (1) and for Ly 1 cells that act as suppression-inducers (SI) (Ly 1 :SI cells) (2, 3), but an entirely communicative partnership has not been ruled out.We now report direct evidence that the Lyl :HE and Lyl :SI cells are derived from the Ly123 set by differentiation, and further incidental evidence of communicative interactions involving Ly123 and Lyl cells.We obtained these data by using genetic markers (Lyt-1 allotypes of Lyt-1 congenic mice) to trace the origin of Lyl:HE and Lyl:SI cells from alternative, allotypedistinguished Ly123 cells, in the cortisone-resistant nylon-purified thymocyte (CRNPT)-macrophage (M~) test system (4) in which antigen-specific Lyl:HE (3) and Lyl:SI (3) cells are generated from CRNPT cultured on peritoneal M~ from specifically primed mice.
Materials and MethodsMice. C57BL/6 (B6) mice (phenotype Lyt-l.2:Lyt-2.2) were obtained from The Jackson Laboratory, Bar Harbor, Maine. Congenie B6-Lyt-1 a mice (phenotype Lyt-1. l:Lyt-2.2) were bred at the Sloan-Kettering Institute, New York.
Antigens. Preparation of group A Streptococcus vaccine (SAV) and its trinitrophenyl (TNP) conjugate (TNP-SAV) is described elsewhere (5, 6).T-M~ Culture. This procedure, in which CRNPT are cultured for 4 d on M~ from donors primed with SAV, yielding mostly Lyl cells (3), whose HE and SI functions are measured by plaque-forming cell (PFC) assay with T-depleted and intact spleen populations, respectively, is described elsewhere (3) and is briefly recapitulated in footnotes to Tables I and III. Selection of Cell Sets from CRNPT. Ly2 + cells (Ly123 and Ly23) were positively selected from B6 and B6-Lyt-1 a CRNPT as follows:Step 1: Incubation of CRNPT with ct-Lyt-2.2 (7) for 30 min on ice (2.5 × 107 CRNPT/ml of 1:50 et-Lyt-2.2 with a cytotoxicity titer of 1:640 against B6 and B6-Lyt-1" thymocytes, both B6 and B6-Lyt-1 a mice being Lyt-2.2).Step 2: Twice-washed antibody-coated cells from step 1 were applied to plastic dishes coated with immunoadsorbent-*
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