Co-evolution of rat TAP transporters and MHC class I RT1-A molecules.
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.
Joly
E
E
Department of Immunology, The Babraham Institute, Cambridge, CB2 4AT, UK. Etienne.Joly@BBSRC.AC.UK
Le Rolle
A F
AF
González
A L
AL
Mehling
B
B
Stevens
J
J
Coadwell
W J
WJ
Hünig
T
T
Howard
J C
JC
Butcher
G W
GW
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
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