A 2 amino acid shift in position leads to a substantial difference in the pattern of processing of 2 HIV-1 epitopes.
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.
Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
Abigail
A
Culshaw
Tao
T
Dong
Sarah Louise
SL
Rowland-Jones
D016915:AIDS Vaccines / Q000276:immunology; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D017951:Antigen Presentation / Q000276:immunology; D002478:Cells, Cultured; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D015488:HIV Antigens / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D059947:HLA-B40 Antigen / Q000276:immunology; D015795:HLA-B8 Antigen / Q000276:immunology; D006801:Humans; D008969:Molecular Sequence Data; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000276:immunology
D016915:AIDS Vaccines; D000939:Epitopes; D015488:HIV Antigens; D059947:HLA-B40 Antigen; D015795:HLA-B8 Antigen; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1