title: Peptide length preferences for rat and mouse MHC class I molecules using random peptide libraries.
abstract: MHC class I molecules bind short peptides for presentation to CD8+ T cells. The determination of the three-dimensional structure of various MHC class I complexes has revealed that both ends of the peptide binding site are composed of polar residues conserved among all human and murine MHC class I sequences, which act to lock the ends of the peptide into the groove. In the rat, however, differences in these important residues occur, suggesting the possibility that certain rat MHC class I molecules may be able to bind and present longer peptides. Here we have studied the peptide length preferences of two rat MHC class Ia molecules expressed in the TAP2-deficient mouse cell line RMA-S: RT1-A1c, which carries unusual key residues at both ends of the groove, and RT1.Aa which carries the canonical residues. Temperature-dependent peptide stabilization assays were performed using synthetic random peptide libraries of different lengths (7-15 amino acids) and successful stabilization was determined by FACS analysis. Results for two naturally expressed mouse MHC class I molecules revealed different length preferences (H2-Kb, 8-13-mer and H2-Db, 9-15-mer peptides). The rat MHC class Ia molecule, RT1-Aa, revealed a preference for 9-15-mer peptides, whereas RT1-A1c showed a more stringent preference for 9-12-mer peptides, thereby ruling out the hypothesis that unusual residues in rat MHC molecules allow binding of longer peptides.
authors.affiliation: Department of Immunology, The Babraham Institute, Cambridge, GB. james.stevens@bbsrc.ac.uk
authors.forename: J
authors.initials: J
authors.lastname: Stevens
authors.forename: K H
authors.initials: KH
authors.lastname: Wiesmüller
authors.forename: P
authors.initials: P
authors.lastname: Walden
authors.forename: E
authors.initials: E
authors.lastname: Joly
mesh_terms: D000818:Animals; D015395:Histocompatibility Antigens Class I / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D051379:Mice; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry; D011487:Protein Conformation; D051381:Rats
chemical_list: D015395:Histocompatibility Antigens Class I; D019151:Peptide Library; D010455:Peptides