Anti‐HLA antigen class I heavy chain monoclonal antibodies inhibit human immunodeficiency virus production by peripheral blood mononuclear cells

Corbeau, Pierre; Olive, Daniel; Devaux, Christian

doi:10.1002/eji.1830210402

Cited by 25 publications

(23 citation statements)

References 52 publications

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“…In line with the involvement of CD59 and CD38 in HIV infection are the findings that AIDS patients display decreased expression of CD59 [36] ,whereas CD38 is highly expressed by CDV cells and almost absent in CD4+ cells [37]. Involvement of HLA class I molecules in viral infection is suggested by the observation that anti-HLA class I antibodies seem to inhibit HIV infectivity [38].…”

Section: Discussionmentioning

confidence: 80%

Modulation of CD4 lateral interaction with lymphocyte surface molecules induced by HIV‐1 gp120

et al. 1995

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CD4, a lymphocyte surface glycoprotein, serves as co-receptor for antigen with the T cell receptor (TCR). It is also the lymphocyte receptor for HIV by binding the gp120 viral envelope protein. Interaction of gp120 with CD4 is crucial for viral infection, but is not sufficient to allow viral entry into cells. Recombinant gp120 alters CD4+ T cell responsiveness to activation stimuli. To express its co-receptor function fully, CD4 must be laterally associated with the TCR and CD45 to form multi-receptor complexes competent to transduce potent activation signals. Here, we examine the possibility that gp120/CD4 binding alters lateral associations of CD4 with other lymphocyte surface molecules, and that assembly of abnormal multi-molecular complexes is involved in the gp120-induced CD4+ T cell dysfunction and in viral entry. In the absence of gp120, CD4 displayed high association with CD3, CD5, CD45RC, CD25, CD28, CD44, and CD53; weak association with CD2, CD38, CD45RB, CD62L, and CD26; and no association with CD45RA, CD45RO, CD11b, CD11a, CD54, CD7, CD48, CD98, CD59 CD55, HLA class I and class II molecules. Treatment with gp120 significantly increased CD4 association with CD3, CD45RA, CD45RB, CD59, CD38, CD26 and HLA class I, and decreased that with CD45RC. Specificity of these results were assessed at various levels. First, gp120 did not influence lateral associations displayed by other molecules, such as HLA class II. Second, the Leu3 mAb which binds CD4 on a site overlapping the gp120 binding site, did not elicit the same CD4 lateral associations as gp120, and finally, a direct gp120/CD4+ interaction was needed to induce the lateral associations, as shown by the observation that blocking the gp120/CD4 binding by the Leu3 mAb inhibited the gp120-induced associations. These results can be interpreted in several ways gp120/CD4 interaction could trigger an inside-out signal responsible for the associations, or gp120 could induce steric modifications of CD4 that increase its affinity for the associating molecules. Alternatively, these molecules may interact directly with gp120, bridging them with CD4. It is also possible that th e associations may be mediated by additional components, interacting with both gp120 and the associating surface molecule. The last hypothesis is likely for CD59, whose gp120-induced association with CD4 required the presence of serum in the co-capping assay. Since both CD59 and gp120 bind complement, the observed association could be mediated by complement components.

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Section: Discussionmentioning

confidence: 80%

Modulation of CD4 lateral interaction with lymphocyte surface molecules induced by HIV‐1 gp120

et al. 1995

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“…Determination of IgG specific for an antigen different from that used for pulsing PBMCs served as controls for immunoglobulin production via noncognate T-B lymphocyte cooperation. IgG anti-CD4 antibodies in the serum of a portion of exposed uninfected individuals In 2 cohorts of 47 EU subjects and 41 HIV-1-seropositive subjects, 16 of 47 (34.0%) and 13 of 41 (31.7%) had A-CD4Ab in serum above the cut-off level, respectively (not shown). The fine specificity of A-CD4Ab was studied in an assay where binding of biotinylated soluble gpl20 to solid-phase CD4 was measured after incubation with each serum in a dilution containing a fixed amount of anti-CD4-binding activity.…”

Section: T Cell Lines and Clonesmentioning

confidence: 86%

“…This allowed us to establish as cutoff for positivity of A-CD4Ab (3 SD above the mean value) the value of 55,530 AU/ml. In a cohort of 54 exposed uninfected subjects, 16 of 47 (34%) had A-CD4Ab in serum above the cutoff level. Further details on this cohort will be reported elsewhere (L. Lopalco et ah, in preparation).…”

Section: Elisasmentioning

confidence: 98%

Human Immunodeficiency Virus Type 1 Glycoprotein 120-Specific T Lymphocytes Provide Intermolecular Help for Anti-CD4 Autoantibody Production in Exposed Uninfected Subjects

Furci¹,

Beretta²,

Siccardi³

et al. 1997

AIDS Research and Human Retroviruses

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Anti-CD4 antibodies have been documented in about 10-20% of HIV-infected patients. This autoimmune response could be triggered by increased CD4 processing and unveiling of hidden (cryptic) epitopes. Multiple markers of exposure to HIV have been described in exposed uninfected individuals. Here, we investigated the mechanisms underlying the generation of anti-CD4 antibodies in a cohort of 54 seronegative exposed uninfected individuals. We identified anti-CD4 antibodies above normal levels in 16 of 47 (34%) exposed uninfected subjects. The fine specificity of these antibodies was different in this cohort when compared with those found in HIV+ patients. This suggested the possibility of different mechanisms underlying the generation of anti-CD4 antibodies in these two groups. Indeed, in exposed uninfected subjects, we found circulating CD4 T cells specific for gp120, but not for CD4. In contrast, HIV-1-seropositive patients had peripheral blood T cells specific for both molecules. Noncovalent binding of gp120 to soluble CD4 enhanced activation of gp120-specific T lymphocytes in exposed uninfected subjects, but not in HIV+ subjects. Moreover, gp120-specific T cells isolated from exposed uninfected, but not from HIV+, subjects provided help for anti-CD4 antibody production by B cells pulsed with CD4-gp120 complex. We conclude that gp120-specific T cells are present in exposed uninfected individuals, and can provide intermolecular help for anti-CD4 antibody production. This mechanism is distinct from that found in HIV-1-seropositive patients and may play a protective role against HIV-1 infection in vivo.

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“…Viral stocks were prepared from the chronically infected CEM cell supernatants as previously described (Corbeau et al, 1991) and kept frozen at -80°C until use. After thawing, 100 ,tl of these stock viruses corresponding to 100 TCID50 (50% Tissue Culture Infective Dose) were used for infection assays.…”

Section: Cells and Virusesmentioning

confidence: 99%

The cytoplasmic domain of CD4 plays a critical role during the early stages of HIV infection in T-cells.

1994

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The role played by the cytoplasmic domain of the CD4 molecule in the process of HIV infection was investigated, using A2.01 cells which express different forms of the CD4 gene. A delay in HIV production was consistently observed in cells expressing a truncated CD4 which lacks the cytoplasmic domain (CD4.401) compared with cells expressing the wild type CD4. The delay was much less in cells expressing a hybrid CD4‐CD8 molecule (amino acids 1‐177 of CD4 fused to the hinge, transmembrane and cytoplasmic domains of CD8). Yet the extent of viral entry and reverse transcription, monitored by semi‐quantitative PCR, was similar in each cell type studied. For further study of the mechanism responsible for delayed HIV replication in the A2.01/CD4.401 cell line, cells were treated with phytohaemagglutinin (PHA), 24 h after HIV infection. Under such experimental conditions HIV production was detected at the same time in the culture supernatants of A2.01/CD4 and A2.01/CD4.401 cells. Moreover, we found that CD4 oligomerization by HIV‐1 induced NF‐kappa B translocation in A2.01/CD4 and A2.01/CD4‐CD8 but not in A2.01/CD4.401 cells. This was consistent with CAT assay experiments which provided evidence for Tat‐independent NF‐kappa B mediated activation of HIV‐1 LTR promoter after HIV binding to CD4 in A2.01/CD4 and A2.01/CD4‐CD8 but not in A2.01/CD4.401 cells. In contrast to results published recently by Tremblay et al. (1994, EMBO J., 13, 774‐783), we propose that a positive cellular signal initiated following oligomerization of the CD4 by the virus itself is involved in NF‐kappa B‐dependent early HIV transcription in A2.01/CD4 cells.

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Anti‐HLA antigen class I heavy chain monoclonal antibodies inhibit human immunodeficiency virus production by peripheral blood mononuclear cells

Cited by 25 publications

References 52 publications

Modulation of CD4 lateral interaction with lymphocyte surface molecules induced by HIV‐1 gp120

Modulation of CD4 lateral interaction with lymphocyte surface molecules induced by HIV‐1 gp120

Human Immunodeficiency Virus Type 1 Glycoprotein 120-Specific T Lymphocytes Provide Intermolecular Help for Anti-CD4 Autoantibody Production in Exposed Uninfected Subjects

The cytoplasmic domain of CD4 plays a critical role during the early stages of HIV infection in T-cells.

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