Binding of 8-mer to 11-mer peptides carrying the anchor residues to slow assembling HLA class I molecules (HLA-B*5101).
The binding of 303 8-mer to 11-mer peptides carrying the anchor residues at P2 and the C-terminus to HLA-B*5101 molecules was examined by a stabilization assay in which peptides were incubated with RMA-S-B*5101 cells at 26 degrees C for 3 h. Analysis of the binding of these peptides to HLA-B*5101 molecules showed that Pro and Ala at P2, and Ile, Val, and Leu at the C-terminus functioned as anchor residues, while Gly at P2 and Met at the C-terminus were weak anchors. Pro was a stronger anchor residue than Ala at P2, while Ile was the strongest anchor at the C-terminus. Among 8-mer to 11-mer peptides, the 9-mer peptides showed the strongest binding to HLA-B*5101 molecules. This is in contrast to our recent findings that 10-mer and 11-mer peptides bind to HLA-B*3501 molecules as effectively as 9-mer peptides. Since both HLA class I molecules have the same B-pocket and the binding peptides carry the same anchor residues, it is assumed that the structure of the F-pocket may restrict the length of binding peptides. The ability of HLA-B*5101 binding peptides to stabilize the HLA-B*5101 molecules was markedly lower than that of HLA-B*3501 binding peptides to stabilize the HLA-B*3501 molecules. It is known that HLA-B*5101 is a slow assembling molecule, while HLA-B*3501 assembles rapidly. The results imply that the slow assembling of HLA-B*5101 molecules results from the low affinity of peptides to HLA-B*5101 molecules.
Sakaguchi
T
T
Department of Tumor Biology, Institute of Medical Science, University of Tokyo, Shirokanedai 4-6-1, Minato-ku, Tokyo 108, Japan.
Ibe
M
M
Miwa
K
K
Kaneko
Y
Y
Yokota
S
S
Tanaka
K
K
Takiguchi
M
M
D002460:Cell Line; D015497:HIV-1 / Q000276:immunology; D015235:HLA-B Antigens / Q000276:immunology*; D016174:Hepacivirus / Q000276:immunology; D006801:Humans; D010455:Peptides / Q000737:chemistry / Q000276:immunology*; D011485:Protein Binding; D013329:Structure-Activity Relationship; D013696:Temperature; D013997:Time Factors; D014764:Viral Proteins / Q000138:chemical synthesis / Q000276:immunology
D015235:HLA-B Antigens; D010455:Peptides; D014764:Viral Proteins