Cutting edge: HLA-B27 acquires many N-terminal dibasic peptides: coupling cytosolic peptide stability to antigen presentation.
Ag presentation by MHC class I is a highly inefficient process because cytosolic peptidases destroy most peptides after proteasomal generation. Various mechanisms shape the MHC class I peptidome. We define a new one: intracellular peptide stability. Peptides with two N-terminal basic amino acids are more stable than other peptides. Such peptides should be overrepresented in the peptidome of MHC class I-associated peptides. HLA-B27 binding peptides use anchor residue R at P2 and, although most amino acids are allowed, particular amino acids are overrepresented at P1, including R and K. We show that such N-terminal dibasic peptides are indeed more efficiently presented by HLA-B27. This suggests that HLA-B27 can present peptides from Ags present in fewer copies than required for successful peptide generation for other MHC class I molecules.
Division of Tumor Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Carla A
CA
Herberts
Joost J
JJ
Neijssen
Jolanda
J
de Haan
Lennert
L
Janssen
Jan Wouter
JW
Drijfhout
Eric A
EA
Reits
Jacques J
JJ
Neefjes
D017951:Antigen Presentation / Q000276:immunology*; D002460:Cell Line; D003600:Cytosol / Q000737:chemistry* / Q000201:enzymology / Q000276:immunology; D015796:HLA-B27 Antigen / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism
D015796:HLA-B27 Antigen; D010446:Peptide Fragments; D010447:Peptide Hydrolases