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Journal of Virology, October 2000, p. 9306-9312, Vol. 74, No. 19
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Immunogenicity of Mutations Induced by Nucleoside Reverse Transcriptase Inhibitors for Human Immunodeficiency Virus Type 1-Specific Cytotoxic T Cells

Assia Samri,1 Gaby Haas,1,2 Joerg Duntze,1 Jean-Marc Bouley,1 Vincent Calvez,3 Christine Katlama,4 and Brigitte Autran1,*

Laboratoire d'Immunologie Cellulaire et Tissulaire, UMR CNRS 7627,1 Laboratoire de Virologie,3 and Département des Maladies Infectieuses,4 Hôpital Pitié-Salpêtrière, 75013 Paris, France, and Max-Planck-Institut für Infektionsbiologie, D-10117 Berlin, Germany2

Received 28 January 2000/Accepted 26 June 2000

The impact of drug resistance mutations induced by nucleoside reverse transcriptase (RT) inhibitors (NRTI) on cytotoxic T-lymphocyte (CTL) recognition of human immunodeficiency virus type 1 strain LAI (HIV-1LAI) RT was addressed in 35 treated or untreated patients. Two HIV-1LAI RT regions encompassing mutation M41L, L74V, M184V, and T215Y/F were recognized in 75 and 83% mutated and in 33 and 42% unmutated samples, respectively. A total of 41 new CTL epitopes overlapping these mutations were predicted. Mutations enhanced HLA-binding scores of 17 epitopes, decreased scores of 5, and had no effect in 19. Four predicted epitopes containing mutations 41, 74, and 184 were tested and recognized by CD8 cells from mutated or unmutated samples, with frequencies up to 270 gamma interferon spot-forming cells per 106 peripheral blood mononuclear cells. Therefore, RT mutations induced by NRTI can increase the immunogenicity of RT for CTL and might allow a better immune control of resistant viruses in vivo, suggesting that specific immune therapy might help prevent these mutations.

* Corresponding author. Mailing address: Laboratoire d'Immunologie Cellulaire et Tissulaire, UMR CNRS 7627, Hôpital Pitié-Salpêtrière, 83 Bd. de l'Hôpital, 75013 Paris, France. Phone: 33 1 42 17 74 03. Fax: 33 1 42 17 74 90. E-mail: brigitte.autran{at}ap-hop-paris.fr.

Journal of Virology, October 2000, p. 9306-9312, Vol. 74, No. 19
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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