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BACKGROUND: The sequence diversity that exists between HIV-1 strains presents a major obstacle to the design of a vaccine that will be effective on a global scale. Focusing on highly conserved cytotoxic T-lymphocyte epitopes as vaccine targets has been called into question by evidence that variation within epitope flanking regions can affect processing and presentation. METHODS: Using epitope-specific T-cell clones tested for recognition of HLA-matched target cells infected with vaccinia viruses expressing HIV-1 nef genes derived from different HIV-1 clades, we examined the efficiency of presentation of an HLA-B*40 restricted HIV-1 nef epitope compared to that of an HLA-B*08 restricted epitope with which it overlaps by 6 amino acides. RESULTS: This small shift in epitope position substantially changed the patter or epitope processing and led either to an increase or decrease in antigen generation dependent on the viral sequences present. CONCLUSIONS: These data demonstrate the complexity of the antigen presentation pathway and the difficulties associated with selecting CTL epitopes as targets for an HIV-1 vaccine that will be effective in many populations and against several viral strains.

Original publication

DOI

10.1097/QAI.0b013e318248780c

Type

Journal article

Journal

J Acquir Immune Defic Syndr

Publication Date

01/04/2012

Volume

59

Pages

335 - 339

Keywords

AIDS Vaccines, Amino Acid Sequence, Amino Acid Substitution, Antigen Presentation, Cells, Cultured, Epitopes, HIV Antigens, HIV-1, HLA-B40 Antigen, HLA-B8 Antigen, Humans, Molecular Sequence Data, T-Lymphocytes, Cytotoxic, nef Gene Products, Human Immunodeficiency Virus