Alternative peptide repertoire of HLA-E reveals a binding motif that is strikingly similar to HLA-A2.
The non-classical HLA-E is a conserved class I molecule that mainly presents monomorphic leader peptides derived from other HLA class I molecules. These leader peptides comprise an optimized sequence for tight and deep binding into the HLA-E groove. In a TAP-deficient environment, as it can be generated during viral infection or in tumor tissue, loading of the classical leader peptide sequences is hampered leading to an alternative HLA-E peptide repertoire. In this study, we characterized this alternative peptide repertoire using cells in which TAP activity is inhibited. We identified more than 500 unique peptide sequences carried by HLA-E and found that their binding motif is different from the dominant leader peptides. Hydrophobic amino acids were only found at positions 2 and 9, in close resemblance to the peptide binding motif of HLA-A*0201. HLA-E-eluted peptides were indeed able to bind this classical HLA class I molecule. Our findings suggest that the dominant leader peptides uniquely conform to HLA-E, but that in their absence a peptide pool is presented like that of HLA-A*0201.
Department of Clinical Oncology, Leiden University Medical Center, The Netherlands.
Margit H
MH
Lampen
Chopie
C
Hassan
Marjolein
M
Sluijter
Annemieke
A
Geluk
Karin
K
Dijkman
Jennifer M
JM
Tjon
Arnoud H
AH
de Ru
Sjoerd H
SH
van der Burg
Peter A
PA
van Veelen
Thorbald
T
van Hall
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000276:immunology / Q000378:metabolism; D020816:Amino Acid Motifs / Q000276:immunology; D000595:Amino Acid Sequence; D017951:Antigen Presentation / Q000276:immunology; D005434:Flow Cytometry; D015789:HLA-A2 Antigen / Q000737:chemistry* / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000737:chemistry* / Q000276:immunology*; D006801:Humans; D020014:K562 Cells; D008969:Molecular Sequence Data; D021382:Protein Sorting Signals / Q000502:physiology; D014162:Transfection; D000097625:HLA-E Antigens
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D015789:HLA-A2 Antigen; D015395:Histocompatibility Antigens Class I; D021382:Protein Sorting Signals; D000097625:HLA-E Antigens; C073119:TAP1 protein, human