title: Co-evolution of rat TAP transporters and MHC class I RT1-A molecules.
abstract: The genes for rat major histocompatibility complex (MHC) class I molecules are associated either with those for the A allele of the transporter associated with antigen processing (TAP-A), which can transport peptides with basic carboxy-terminal residues, or with those for TAP-B, which cannot [1-5]. To explore whether these associations have a functional basis, we compared the sequences of 13 rat MHC class la RT1-A cDNAs from nine MHC haplotypes. Of seven TAP-A- linked RT1-A molecules, six possess strongly acidic F pockets, and these bind a high proportion of peptides with basic carboxy-terminal residues. The F pockets of TAP-B-linked molecules, by contrast, were more basic. Furthermore, we identified six positions at the 'righthand end' of the peptide-binding groove, at which a majority of TAP-B-linked molecules diverge from the consensus sequence for class la molecules whereas, at these positions, all the TAP-A-linked molecules reflect the consensus sequence. Our results suggest that the linked rat class la and TAP genes have co-evolved to maximize the supply of appropriate peptides to the presenting molecules.
authors.affiliation: Department of Immunology, The Babraham Institute, Cambridge, CB2 4AT, UK. Etienne.Joly@BBSRC.AC.UK
authors.forename: E
authors.initials: E
authors.lastname: Joly
authors.forename: A F
authors.initials: AF
authors.lastname: Le Rolle
authors.forename: A L
authors.initials: AL
authors.lastname: González
authors.forename: B
authors.initials: B
authors.lastname: Mehling
authors.forename: J
authors.initials: J
authors.lastname: Stevens
authors.forename: W J
authors.initials: WJ
authors.lastname: Coadwell
authors.forename: T
authors.initials: T
authors.lastname: Hünig
authors.forename: J C
authors.initials: JC
authors.lastname: Howard
authors.forename: G W
authors.initials: GW
authors.lastname: Butcher
mesh_terms: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000483:Alleles; D000818:Animals; D017951:Antigen Presentation; D019143:Evolution, Molecular; D005805:Genes, MHC Class I; D006239:Haplotypes / Q000235:genetics; D006649:Histocompatibility Antigens / Q000737:chemistry / Q000235:genetics*; D008958:Models, Molecular; D011487:Protein Conformation; D051381:Rats / Q000235:genetics* / Q000276:immunology
chemical_list: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D006649:Histocompatibility Antigens; C073119:TAP1 protein, human; C486172:Tap1 protein, rat; C489514:Tap2 protein, rat; C038353:histocompatibility antigens RT, rat; C071692:TAP2 protein, human