Cytotoxic T lymphocytes recognize structurally diverse, clade-specific and cross-reactive peptides in human immunodeficiency virus type-1 gag through HLA-B53.

Journal article

Human immunodeficiency virus type-1 (HIV-1) cytotoxic T lymphocyte (CTL) epitopes have largely been defined in Caucasian populations infected with clade B virus. Identification of potentially protective CTL epitopes in non-B clade-infected African subjects is important for vaccine development. In a study of CTL responses in clade A-infected Gambians, using cytotoxicity, interferon-gamma (IFN-gamma) enzyme-linked immunospot (ELISpot) and HLA-B53-peptide tetramer assays, we identified three HLA-B53-restricted epitopes in HIV-1 gag p24. CTL specific for an epitope in a highly immunogenic region of the p24 protein showed no cross-reactivity to other HIV-1 clades. Two of the epitopes would not have been predicted from the peptide-binding motif due to the absence of a proline anchor at position 2. Structural analysis of HLA-B53 and its relative, HLA B35, enabled us to re-define the peptide-binding motif to include other P2 anchors. These results demonstrate the value of combined immunological and structural analyses in defining novel CTL epitopes and have implications for HIV-1 vaccine design.

Authors: Dorrell, L; Willcox, B; Jones, E; Gillespie, G; Njai, H

• Publication status: Published
• Journal: European journal of immunology
• Volume: 31
• Issue: 6
• Pages: 1747-1756
• Publication date: 2001-06-01
• DOI: 10.1002/1521-4141(200106)31:6<1747::aid-immu1747>3.3.co;2-c
• EISSN: 1521-4141
• ISSN: 0014-2980
• Language: English
• Keywords: Molecular Sequence Data; T-Lymphocytes, Cytotoxic; HIV-2; HIV Core Protein p24; Viral Proteins; HLA Antigens; HIV Antigens; HIV-1; Cell Line, Transformed; Gene Products, gag; Humans; Cross Reactions; Amino Acid Sequence; Peptides; Epitopes, T-Lymphocyte; HIV Infections; gag Gene Products, Human Immunodeficiency Virus