Cross-linking of Fas by antibodies to a peculiar domain of gp120 V3 loop can enhance T cell apoptosis in HIV-1-infected patients

Franco Silvestris, Shigekazu Nagata, Paola Cafforio, Nicola Silvestris, Franco Dammacco

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Previous studies have demonstrated that T cell reactive antibodies in HIV-1 infection contribute to lymphocyte depletion by cytotoxicity that involves differential membrane targets, such as the 43.5-kD receptor on CEM cells. Here, we show that these antibodies bind Fas as result of a molecular mimicry of the gp120. Both flow cytometry and immunoblotting using the human Fas-transfected mouse WC8 lymphoma revealed positive binding of immunoglobulin G from several patients to a 43.8-kD membrane receptor that also reacts with the CH11 anti-Fas monoclonal antibody. Specificity to Fas was further confirmed to chimeric recombinant human Fas-Fc by ELISA, whereas overlapping peptide mapping of a Fas domain (VEINCTR-N) shared by gp120 V3 loop demonstrated a predominant affinity to the full-length 10-mer peptide. Four anti-Fas affinity preparations greatly increased the subdiploid DNA peak of CEM cells similar to agonist ligands of Fas. In addition, anti-Fas immunoglobulin G strongly inhibited the [3H]thymidine uptake of CEM cells in proliferative assays, inducing a suppression as high as provoked by both CH11 mAb and recombinant human Fas ligand. Since anti-Fas were reactive to gp120, it is conceivable that antibodies binding that domain within the V3 region are effective cross-linkers of Fas and increase apoptosis in peripheral T cells. These results suggest that autologous stimulation of the Fas pathway, rather than of lymphocytotoxic antibodies, may aggravate lymphopenia in a number of HIV-1+ subjects.

Original languageEnglish
Pages (from-to)2287-2300
Number of pages14
JournalJournal of Experimental Medicine
Volume184
Issue number6
DOIs
Publication statusPublished - Dec 1 1996

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HIV-1
Fas Ligand Protein
anti-Fas monoclonal antibody
Apoptosis
T-Lymphocytes
Antibodies
Immunoglobulin G
Lymphocyte Depletion
Molecular Mimicry
Lymphopenia
Peptide Mapping
Antilymphocyte Serum
Membranes
Immunoblotting
Thymidine
HIV Infections
Lymphoma
Flow Cytometry
Enzyme-Linked Immunosorbent Assay
Peptides

ASJC Scopus subject areas

  • Immunology

Cite this

Cross-linking of Fas by antibodies to a peculiar domain of gp120 V3 loop can enhance T cell apoptosis in HIV-1-infected patients. / Silvestris, Franco; Nagata, Shigekazu; Cafforio, Paola; Silvestris, Nicola; Dammacco, Franco.

In: Journal of Experimental Medicine, Vol. 184, No. 6, 01.12.1996, p. 2287-2300.

Research output: Contribution to journalArticle

Silvestris, Franco ; Nagata, Shigekazu ; Cafforio, Paola ; Silvestris, Nicola ; Dammacco, Franco. / Cross-linking of Fas by antibodies to a peculiar domain of gp120 V3 loop can enhance T cell apoptosis in HIV-1-infected patients. In: Journal of Experimental Medicine. 1996 ; Vol. 184, No. 6. pp. 2287-2300.
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