Tapasin enhances MHC class I peptide presentation according to peptide half-life.
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.
Medical Research Council Human Immunology Unit, Oxford University, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom.
Mark
M
Howarth
Anthony
A
Williams
Anne B
AB
Tolstrup
Tim
T
Elliott
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000276:immunology; D017951:Antigen Presentation; D017920:Antiporters / Q000502:physiology*; D037282:Calreticulin / Q000502:physiology; D002460:Cell Line; D006207:Half-Life; D006360:Heat-Shock Proteins / Q000502:physiology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007136:Immunoglobulins / Q000502:physiology*; D007535:Isomerases / Q000502:physiology; D026901:Membrane Transport Proteins; D051379:Mice; D018345:Mice, Knockout; D010455:Peptides / Q000276:immunology*; D019704:Protein Disulfide-Isomerases
D000906:Antibodies; D017920:Antiporters; D037282:Calreticulin; D006360:Heat-Shock Proteins; D015395:Histocompatibility Antigens Class I; D007136:Immunoglobulins; D026901:Membrane Transport Proteins; D010455:Peptides; C107762:tapasin; D007535:Isomerases; C513195:Pdia3 protein, mouse; D019704:Protein Disulfide-Isomerases; C085868:PDIA3 protein, human