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Journal of Virology, August 2000, p. 7678-7682, Vol. 74, No. 16
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Immune Response to Recombinant Adenovirus in Humans: Capsid Components from Viral Input Are Targets for Vector-Specific Cytotoxic T Lymphocytes

Valérie Molinier-Frenkel,1,dagger Hanne Gahery-Segard,2 Majid Mehtali,3 Christophe Le Boulaire,1 Sébastien Ribault,3 Pierre Boulanger,4 Thomas Tursz,1 Jean-Gérard Guillet,2 and Françoise Farace1,*

Départements de Biologie Clinique ou de Médecine, Institut Gustave Roussy, 94805 Villejuif,1 Laboratoire d'Immunologie des Pathologies Infectieuses et Tumorales, INSERM U445, Institut Cochin de Génétique Moléculaire, Université R. Descartes, Hôpital Cochin, 75014 Paris,2 Transgène S.A., 67000 Strasbourg,3 and Laboratoire de Virologie et Pathogénèse Virale, CNRS UMR 5537, Faculté de Médecine RTH Laennec, 69008 Lyon,4 France

Received 30 March 2000/Accepted 17 May 2000

We previously demonstrated that a single injection of 109 PFU of recombinant adenovirus into patients induces strong vector-specific immune responses (H. Gahéry-Ségard, V. Molinier-Frenkel, C. Le Boulaire, P. Saulnier, P. Opolon, R. Lengagne, E. Gautier, A. Le Cesne, L. Zitvogel, A. Venet, C. Schatz, M. Courtney, T. Le Chevalier, T. Tursz, J.-G. Guillet, and F. Farace, J. Clin. Investig. 100:2218-2226, 1997). In the present study we analyzed the mechanism of vector recognition by cytotoxic T lymphocytes (CTL). CD8+ CTL lines were derived from two patients and maintained in long-term cultures. Target cell infections with E1-deleted and E1-plus E2-deleted adenoviruses, as well as transcription-blocking experiments with actinomycin D, revealed that host T-cell recognition did not require viral gene transcription. Target cells treated with brefeldin A were not lysed, indicating that viral input protein-derived peptides are associated with HLA class I molecules. Using recombinant capsid component-loaded targets, we observed that the three major proteins could be recognized. These results raise the question of the use of multideleted adenoviruses for gene therapy in the quest to diminish antivector CTL responses.

* Corresponding author. Mailing address: Département de Biologie Clinique, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, France. Phone: 33 1 42114478. Fax: 33 1 42115268. E-mail: farace{at}igr.fr.

dagger Present address: Laboratoire d'Immunologie des Pathologies Infectieuses et Tumorales, INSERM U445, Institut Cochin de Génétique Moléculaire, Université R. Descartes, Hôpital Cochin, 75014 Paris, France.

Journal of Virology, August 2000, p. 7678-7682, Vol. 74, No. 16
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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