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

Laura Sesma, Begoña Galocha, Miriam Vázquez, Anthony W. Purcell, Miguel Marcilla, James McCluskey, José A. López De Castro

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16 Citations (Scopus)


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 β2-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.

Original languageEnglish
Pages (from-to)7833-7844
Number of pages12
JournalJournal of Immunology
Issue number12
Publication statusPublished - 15 Jun 2005
Externally publishedYes

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