Minimal epitopes expressed in a recombinant polyepitope protein are processed and presented to CD8+ cytotoxic T cells: implications for vaccine design.
The epitopes recognized by CD8+ cytotoxic T lymphocytes (CTL) are generated from cytosolic proteins by proteolytic processing. The nature of the influences exerted by the sequences flanking CTL epitopes on these processing events remains controversial. Here we show that each epitope within an artificial polyepitope protein containing nine minimal CD8+ CTL epitopes in sequence was processed and presented to appropriate CTL clones. Natural flanking sequences were thus not required to direct class I proteolytic processing. In addition, unnatural flanking sequences containing other CTL epitopes did not interfere with processing. The ability of every CTL epitope to be effectively processed from a protein containing only CTL epitopes is likely to find application in the construction of recombinant polyepitope CTL vaccines.
Thomson
S A
SA
Queensland Institute of Medical Research, P.O. Box Royal Brisbane Hospital, Australia.
Khanna
R
R
Gardner
J
J
Burrows
S R
SR
Coupar
B
B
Moss
D J
DJ
Suhrbier
A
A
D000595:Amino Acid Sequence; D000956:Antigens, Viral / Q000276:immunology*; D002999:Clone Cells; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000276:immunology*; D015195:Drug Design; D000939:Epitopes / Q000096:biosynthesis / Q000276:immunology*; D019309:Epstein-Barr Virus Nuclear Antigens; D006680:HLA Antigens / Q000276:immunology; D015234:HLA-A Antigens / Q000276:immunology; D015235:HLA-B Antigens / Q000276:immunology; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014614:Vaccines, Synthetic; D014616:Vaccinia virus / Q000276:immunology*; D014765:Viral Vaccines
D000956:Antigens, Viral; D017931:DNA Primers; D004268:DNA-Binding Proteins; D000939:Epitopes; D019309:Epstein-Barr Virus Nuclear Antigens; D006680:HLA Antigens; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; D014765:Viral Vaccines