1. ¹Department of Histology, Microbiology and Medical Biotechnologies, Section of Microbiology and Virology, University of Padova, Padova, Italy
2. ²Department of Biochemistry and Molecular Biology, University of Ferrara, Ferrara, Italy
3. ³Department of Molecular Biology, Virology Section, University of Siena, Siena, Italy
4. ⁴Department of Biology and Genetics, University of Milano, Milano, Italy
5. ⁵Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA, USA

Correspondence: Professor G Palù and Professor C Parolin, Department of Histology, Microbiology and Medical Biotechnologies, Section of Microbiology and Virology, University of Padova, Via A Gabelli 63, Padova 35121, Italy

Received 11 May 2004; Accepted 5 September 2004; Published online 21 October 2004.

Abstract

Immune-based approaches of cell therapy against viral pathogens such as the human immunodeficiency virus type 1 (HIV-1) could be of primary importance for the control of this viral infection. Here, we designed a chimeric cell surface receptor (105TCR) to provide primary human T-lymphocytes with antibody-type specificity for the HIV-1 envelope glycoprotein. This receptor includes the single chain Fv domain of the neutralizing anti-gp120 human monoclonal antibody F105, CD8 hinge and the transmembrane and the cytoplasmic domains of TCR. Our results show that 105TCR is expressed at the cellular surface and is capable of recognizing the HIV-1 envelope glycoprotein inducing highly efficient effector T-cell responses, including extracellular signal-regulated kinase phosphorylation and cytokine secretion. Moreover, human primary CD8+ T-lymphocytes transduced by oncoretroviral and lentiviral vectors containing the 105TCR gene are able to mediate in vitro-specific cytolysis of envelope-expressing cells and HIV-1-infected CD4+ T-lymphocytes. These findings suggest that 105TCR is particularly suited for in vivo efficacy studies.