Tapasin enhances MHC class I peptide presentation according to peptide half-life.

Journal article

Understanding how peptides are selected for presentation by MHC class I is crucial to vaccination strategies based on cytotoxic T lymphocyte priming. We have studied this selection of the MHC class I peptide repertoire in terms of the presentation of a series of individual peptides with a wide range of binding to MHC class I. This series was expressed as minigenes, and the presentation of each peptide variant was determined with the same MHC class I peptide-specific antibody. In wild-type cells, the hierarchy of presentation followed peptide half-life. This hierarchy broke down in cells lacking tapasin but not in cells lacking calreticulin or in cells lacking transporter associated with antigen processing-associated ERp57. We demonstrate a key role for tapasin in shaping the MHC class I peptide repertoire, as enhancement of presentation in the presence of tapasin correlated with peptide half-life.

Authors: Howarth, M; Williams, A; Tolstrup, AB; Elliott, T

• Publication status: Published
• Journal: Proceedings of the National Academy of Sciences of the United States of America
• Volume: 101
• Issue: 32
• Pages: 11737-11742
• Publication date: 2004-08-01
• DOI: 10.1073/pnas.0306294101
• EISSN: 1091-6490
• ISSN: 0027-8424
• Language: English
• Keywords: Histocompatibility Antigens Class I; Cell Line; Mice, Knockout; Antiporters; Immunoglobulins; Antigen Presentation; Calreticulin; Mice; Antibodies; Amino Acid Sequence; Membrane Transport Proteins; Animals; Protein Disulfide-Isomerases; Peptides; Isomerases; Humans; Heat-Shock Proteins; Half-Life