title: Gene activating and proapoptotic potential are independent properties of different CD4 epitopes.
abstract: CD4 engagement triggers an early signaling cascade which initiates late events such as transcription factor activation. The outcome of CD4 engagement is T-cell commitment to alternative, dramatically different fates, such as activation and apoptosis. We have tested a panel of anti-CD4 mAbs specific for different CD4 epitopes, as well as HIV-1 gp120, for the capacity to activate crucial early events such as enhancement of p56(lck) kinase activity and Shc phosphorylation. The same CD4 epitopes were characterized for their capacity both to deliver a gene activating signal and to program T-cells to activation dependent death. No correlation could be found between capacity of specific CD4 epitopes to deliver a gene activating signal and capacity to prime T-cells to apoptosis, suggesting that gene activating and proapoptotic potential are independent functions of CD4 epitopes. Furthermore, while triggering of the calcium pathway appears critical in NF-AT activation, optimal p56(lck) activation and Shc phosphorylation might be required for initiation of the apoptotic pathway.
authors.affiliation: Department of Evolutionary Biology, University of Siena, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Milia
authors.forename: M M
authors.initials: MM
authors.lastname: Di Somma
authors.forename: M B
authors.initials: MB
authors.lastname: Majolini
authors.forename: C
authors.initials: C
authors.lastname: Ulivieri
authors.forename: F
authors.initials: F
authors.lastname: Somma
authors.forename: E
authors.initials: E
authors.lastname: Piccolella
authors.forename: J L
authors.initials: JL
authors.lastname: Telford
authors.forename: C T
authors.initials: CT
authors.lastname: Baldari
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000502:physiology; D017209:Apoptosis / Q000276:immunology*; D015704:CD4 Antigens / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000939:Epitopes / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D005786:Gene Expression Regulation / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000494:pharmacology; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000235:genetics; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D015398:Signal Transduction / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D004268:DNA-Binding Proteins; D000939:Epitopes; D015699:HIV Envelope Protein gp120; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D014157:Transcription Factors