Human T-cell lymphotropic virus IIIB glycoprotein (gp120) bound to CD4 determinants on normal lymphocytes and expressed by infected cells serves as target for immune attack.

Abstract

The lymphocyte differentiation antigen CD4 serves as a receptor for human retroviruses associated with acquired immunodeficiency syndrome (AIDS) through its interaction with the major envelope virion glycoprotein, gpl20, which is also expressed on the surface of infected cells. In these experiments, purified gpl20 was shown to bind to normal human T-lymphocyte populations. The gpl2O-CD4 complex served as a target antigen for antibody-dependent complementmediated cytolysis by a goat serum raised against native gpl20. However, patient sera that bound to gpl20-adsorbed cells failed to direct their destruction in the presence of complement. In contrast, these sera were potent mediators of antibodydependent cellular cytotoxicity. These studies demonstrate that gpl20 situated on the cell surface can serve as an effective target for immune destruction by patient antibodies and effector lymphocytes. The possible contribution of this type of immunity to control of disease progression, on the one hand, and to lymphocyte destruction and immunopathology observed in AIDS, on the other, is discussed.The most profound hematologic feature associated with acquired immunodeficiency syndrome (AIDS) is the functional impairment and quantitative depletion of the subset of lymphocytes that express the CD4 surface antigen (1-6). Infection of CD4 cells in vitro results in the rapid spread of virus throughout the culture and subsequent cell death due to the as yet undefined process of virus-induced cytopathology (7)(8)(9)(10)(11)(12) The current body of evidence suggests that the T-cell lymphotropic properties of the causative agent virus are due, in large part, to the interaction between the major virion envelope glycoprotein (gp120) and specific epitopes of the CD4 antigen complex. Monoclonal antibodies directed against particular determinants of CD4 have been shown to block both infection (14, 15) and multinucleated giant cell formation (16), in addition to precipitating gpl2O-CD4 complexes from infected cells (17). Recent studies revealed that purified gpl20 can effectively block cell fusion, most likely by competing for available CD4 sites on noninfected cells (18). In addition, purified gpl20 readily associates with the CD4 molecules and forms a stable complex on the cell surface (19). This latter finding suggested the possibility that free gpl20 bound to noninfected CD4-expressing lymphocytes could serve as a potential target for immune attack resulting in subsequent lympholysis. MATERIALS AND METHODSCells. Normal CD4-positive lymphocyte populations (CD4 cells) were obtained by stimulating normal donor peripheral blood mononuclear cells with tetanus toxoid for 5 days, sorting for CD4 expression, and expanding in the presence of recombinant interleukin 2. CEM cell lines (CEM) or human T-cell lymphotropic virus IIIB (HTLV-IIIB)t chronically infected CEM (CEM/IIIB) have been described (19). gpl20 and Goat gpl2O Antisera. The gp120 was isolated from HTLV-IIIn-infected H9 cells as described (18). Briefly, cells were lysed with...

Immunological studies of the basis for the apathogenicity of simian immunodeficiency virus from African green monkeys.

“…In terms of cell-mediated immunity, PBLs from seropositive AGMs proliferate only poorly in response to inactivated viral antigen (data not shown), similar to the situation with HIVinfected humans (18). Infected humans develop a surprisingly good cytotoxic T-lymphocyte response (19) (20). However, infected AGMs also develop an active ADCC system, they have a strong antibody binding response to envelope proteins, and, like HIV, the target molecule for SIVa is the simian analogue ofthe CD4 molecule (4) phages are to HIV-1 infection.…”

Immunological reactivity of a human immunodeficiency virus type I derived peptide representing a consensus sequence of the GP 120 major neutralizing region V3

“…The characterization of the V3-1oop as an ADCC-target region (aa 315-329) is of special interest with respect to the induction of immune response capable to eliminate HIV-infected cells [ 17,18]. Further, a HIV-1/IIIB derived minimal peptide of gp 120/V3 was shown to be recognized as target for cellular immune response in BALB/c mice immunized with IIIB-env recombinant vaccinia virus [27][28][29].…”

Antibody-Dependent Cellular Cytotoxicity via Humoral Immune Epitope of Nef Protein Expressed on Cell Surface

“…It has been described that gp120 or gp120/41-specific ADCC correlates with rate of disease progression (19,21). But, in contrast, ADCC via envelope proteins could potentially kill the uninfected CD4 ϩ T cells with free viral envelopes on their surface, and therefore ADCC could contribute to depletion of CD4 ϩ T cells and AIDS pathogenesis (22,23). In addition, gp120 is prone to high frequency of mutations; thereby, viral escape mutants may evolve easily (24 -26).…”