Qualitative and Quantitative Differences in Peptides Bound to HLA-B27 in the Presence of Mouse versus Human Tapasin Define a Role for Tapasin as a Size-Dependent Peptide Editor

• Published in: The Journal of immunology (1950) 2005-06, Vol.174 (12), p.7833-7844
• Main Authors: Sesma, Laura, Galocha, Begona, Vazquez, Miriam, Purcell, Anthony W, Marcilla, Miguel, McCluskey, James, de Castro, Jose A. Lopez
• Format: Article
• Language: English
• Subjects: Animals; Antigen Presentation - genetics; Antiporters - biosynthesis; Antiporters - chemistry; Antiporters - genetics; Antiporters - physiology; Cell Line, Transformed; Cell Line, Tumor; Cell Membrane - immunology; Cell Membrane - metabolism; HLA-B Antigens - chemistry; HLA-B Antigens - genetics; HLA-B Antigens - metabolism; HLA-B27 Antigen; Humans; Immunoglobulins - biosynthesis; Immunoglobulins - chemistry; Immunoglobulins - genetics; Immunoglobulins - physiology; Ligands; Membrane Transport Proteins; Mice; Molecular Chaperones - biosynthesis; Molecular Chaperones - chemistry; Molecular Chaperones - genetics; Molecular Chaperones - physiology; Oligopeptides - chemistry; Oligopeptides - genetics; Oligopeptides - metabolism; Protein Binding - genetics; Protein Binding - immunology; RNA Editing - immunology; Species Specificity; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Transfection
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.174.12.7833

Tapasin (Tpn) is a chaperone of the endoplasmic reticulum involved in peptide loading to MHC class I proteins. The influence of mouse Tpn (mTpn) on the HLA-B*2705-bound peptide repertoire was analyzed to characterize the species specificity of this chaperone. B*2705 was expressed on Tpn-deficient human 721.220 cells cotransfected with human (hTpn) or mTpn. The heterodimer to beta(2)-microglobulin-free H chain ratio on the cell surface was reduced with mTpn, suggesting lower B*2705 stability. The B*2705-bound peptide repertoires loaded with hTpn or mTpn shared 94-97% identity, although significant differences in peptide amount were observed in 16-17% of the shared ligands. About 3-6% of peptides were bound only with either hTpn or mTpn. Nonamers differentially bound with mTpn had less suitable anchor residues and bound B*2705 less efficiently in vitro than those loaded only with hTpn or shared nonamers. Decamers showed a different pattern: those found only with mTpn had similarly suitable residues as shared decamers and bound B*2705 with high efficiency. Peptides differentially presented by B*2705 on human or mouse cells showed an analogous pattern of residue suitability, suggesting that the effect of mTpn on B*2705 loading is comparable in both cell types. Thus, mTpn has quantitative and qualitative effects on the B*2705-bound peptide repertoire, impairing presentation of some suitable ligands and allowing others with suboptimal anchor residues and lower affinity to be presented. Our results favor a size-dependent peptide editing role of Tpn for HLA-B*2705 that is species-dependent and suboptimally performed, at least for nonamers, by mTpn.