Fine-specificity of cytotoxic T lymphocytes which recognize conserved epitopes of the Gag protein of human immunodeficiency virus type 1

van Baalen, Carel A., Klein, Michel R., Huisman, Robin C., Dings, Marlinda E. M., Garde, Susana R. Kerkhof, Geretti, Anna Maria, Gruters, Rob, van Els, Cecile A. C. M., Miedema, Frank, Osterhaus, Albert D. M. E.

Abstract

^¹ Institute of Virology, Erasmus University, PO Box 1738, 3000 DR Rotterdam, The Netherlands
^² Department of Clinical Viro-Immunology, The Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam, The Netherlands
^³ Department of Vaccine Development and Immune Mechanisms, National Institute of Public Health and Environmental Protection, Bilthoven, The Netherlands
^⁴ UMR103, CNRS/Biomerieux, Lyon, France

Human immunodeficiency virus type 1 (HIV-1) Gag-specific cytotoxic T lymphocyte (CTL) responses were studied in seven seropositive long-term asymptomatic individuals (CDC A1) with stable CD4 counts for more than 8 years. Using a set of partially overlapping peptides covering the whole Gag, five 1520-mer peptides were found to contain CTL epitopes. Further characterization of these epitopes revealed a new HLA-A25-restricted CTL epitope in p24, p24₂₀₃₂₁₂ ETINEEAAEW. This region of Gag is highly conserved in clades B and D of HIV-1. Naturally occurring amino acid sequences, containing p24₂₀₃D (consensus HIV-1 clades A, C, F, G and H) or p24₂₀₄I (HIV-2_ROD) were not recognized by CTL recognizing the index peptide. No virus variants with mutations in this sequence were found in peripheral blood mononuclear cells from the HIV-1-infected individual concerned during the 8 year observation period, indicating that the virus had not escaped from the observed CTL response.