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CTL recognize short peptide fragments presented by class I MHC molecules. In this study, we examined the effect of phosphorylation on TAP transport, binding to class I MHC molecules, and recognition by CTL of peptide fragments from known phosphorylated oncogene proteins or virus phosphoproteins. We show that phosphopeptides can be efficiently transported from the cytosol to the endoplasmic reticulum by the TAP. Furthermore, we show that phosphorylation can have a neutral, negative, or even a positive effect on peptide binding to class I MHC. Finally, we have generated phosphopeptide-specific CTL that discriminate between the phosphorylated and the nonphosphorylated versions of the peptide. We conclude that phosphopeptide-specific CTL responses are likely to constitute a subset of the class I MHC-restricted CTL repertoire in vivo.

Type

Journal article

Journal

Journal of immunology (Baltimore, Md. : 1950)

Publication Date

10/1999

Volume

163

Pages

3812 - 3818

Addresses

Institute of Cancer Biology, Danish Cancer Society, Copenhagen.

Keywords

T-Lymphocytes, Cytotoxic, Cell Line, Transformed, Tumor Cells, Cultured, Animals, Mice, Inbred C57BL, Humans, Mice, Oligopeptides, Phosphopeptides, ATP-Binding Cassette Transporters, Histocompatibility Antigens Class I, H-2 Antigens, HLA Antigens, Epitopes, T-Lymphocyte, Cytotoxicity Tests, Immunologic, Antigen Presentation, Protein Binding, Phosphorylation, ATP Binding Cassette Transporter, Subfamily B, Member 2