The Ick protein tyrosine kinase is not involved in antibody-mediated CD4 (CDR3-loop) signal transduction that inhibits HIV-1 transcription.

Important note: Information in this article was accurate in 1998. The state of the art may have changed since the publication date.

The Ick protein tyrosine kinase is not involved in antibody-mediated CD4 (CDR3-loop) signal transduction that inhibits HIV-1 transcription.

Eur J Immunol. 1998 May;28(5):1445-57. Unique Identifier : AIDSLINE MED/98264612
Coudronniere N; Corbeil J; Robert-Hebmann V; Mesnard JM; Devaux C; CRBM/CNRS UPR 1086-Laboratoire Infections retrovirales et; signalisation cellulaire, Montpellier, France.

Abstract: Monoclonal antibodies (mAb) that bind to the immunoglobulin CDR3-like region in the D1 domain of the CD4 molecule can inhibit the HIV-1 life cycle in CD4-positive T cells and lymphoblastoid cell lines at the stage of transcription. This antiviral effect requires the integrity of the cytoplasmic tail of CD4 which is known to act as a signal transduction region through its association with the protein tyrosine kinase (PTK) p56lck. In this study, we investigated the putative role of this PTK in transducing inhibitory signals that act on HIV-1 replication after triggering by anti-CDR3-like region antibody treatment of infected T cell lines. CEM (CD4+/p56lck + inducible), MT2 CD4+/p56lck - repressed), HSB-2 (CD4-/p56lck + constitutively), HSB-2 WTCD4 (CD4+/p56lck + constitutively), HSB-2 CD4.402 (CD4+ truncated form which lacks the cytoplasmic domain/p56lck + constitutively), and HSB-2 CD4mut (CD4+ unable to bind lck/p56lck constitutively) were exposed to HIV-1 and cultured in medium supplemented with an anti-CDR3-like region-specific antibody or a control anti-CD4 mAb which does not inhibit HIV-1 transcription. We found that CDR3-loop-mediated inhibitory signals are efficiently transduced in CD4-positive cells which demonstrate a constitutive activation of p56lck or in CD4-positive cells lacking p56lck expression. Moreover, inhibitory signals were transduced in HSB-2 CD4mut cells expressing a cell surface CD4 with a double cysteine mutation in its cytoplasmic tail that renders the molecule unable to bind p56lck, but not HSB-2 CD4.402 cells expressing a truncated form of CD4 which lacks the cytoplasmic domain. These results indicate that the p56lck plays no direct role in this process and suggests the existence of another signaling partner for CD4.

Keywords: *Anti-HIV Agents/IMMUNOLOGY *Antibodies, Monoclonal/PHARMACOLOGY *Antigens, CD4/IMMUNOLOGY *Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/IMMUNOLOGY *Receptor-CD3 Complex, Antigen, T-Cell/IMMUNOLOGY *Signal Transduction/IMMUNOLOGY *Trans-Activation (Genetics)/IMMUNOLOGY
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