title: The rat cim effect: TAP allele-dependent changes in a class I MHC anchor motif and evidence against C-terminal trimming of peptides in the ER.
abstract: Functional polymorphism in the rat peptide transporter associated with antigen processing (TAP) changes the peptide pool available for binding and presentation by a class I MHC allele, RT1.Aa. The peptide binding motif for RT1.Aa, determined by stabilization with synthetic peptides, included a strong preference for arginine at the peptide C terminus. Analysis of natural peptides bound to RT1.Aa by both pool sequencing and anhydrotrypsin chromatography revealed that TAP polymorphism determined the presence or absence of arginine as the peptide C-terminal residue. This result highlights the in vivo impact of TAP-peptide selectivity, and provides evidence against a high rate of generation of new C termini by protease activity in the endoplasmic reticulum.
authors.affiliation: Department of Immunology, The Babraham Institute, Cambridge, United Kingdom.
authors.forename: S J
authors.initials: SJ
authors.lastname: Powis
authors.forename: L L
authors.initials: LL
authors.lastname: Young
authors.forename: E
authors.initials: E
authors.lastname: Joly
authors.forename: P J
authors.initials: PJ
authors.lastname: Barker
authors.forename: L
authors.initials: L
authors.lastname: Richardson
authors.forename: R P
authors.initials: RP
authors.lastname: Brandt
authors.forename: C J
authors.initials: CJ
authors.lastname: Melief
authors.forename: J C
authors.initials: JC
authors.lastname: Howard
authors.forename: G W
authors.initials: GW
authors.lastname: Butcher
mesh_terms: D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000737:chemistry* / Q000235:genetics* / Q000502:physiology; D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics; D010450:Endopeptidases; D004721:Endoplasmic Reticulum / Q000201:enzymology / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D002352:Carrier Proteins; D015395:Histocompatibility Antigens Class I; D010455:Peptides; C489514:Tap2 protein, rat; D010450:Endopeptidases