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Naturally processed non-canonical HLA-A*02:01 presented peptides

Hassan, Chopie, Chabrol, Eric, Jahn, Lorenz, Kester, Michel G.D., de Ru, Arnoud H., Drijfhout, Jan W., Rossjohn, Jamie, Falkenburg, J.H. Frederik, Heemskerk, Mirjam H.M., Gras, Stephanie and van Veelen, Peter A. 2014. Naturally processed non-canonical HLA-A*02:01 presented peptides. The Journal of Biological Chemistry 290 (5) , pp. 2593-2603. 10.1074/jbc.M114.607028

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Human leukocyte antigen (HLA) class I molecules generally present peptides (p) of 8 to 11 amino acids (aa) in length. Although an increasing number of examples with lengthy (>11 aa) peptides, presented mostly by HLA-B alleles, have been reported. Here we characterize HLA-A*02:01 restricted, in addition to the HLA-B*0702 and HLA-B*4402 restricted, lengthy peptides (>11 aa) arising from the B-cell ligandome. We analyzed a number of 15-mer peptides presented by HLA-A*02:01, and confirmed pHLA-I formation by HLA folding and thermal stability assays. Surprisingly the binding affinity and stability of the 15-mer epitopes in complex with HLA-A*02:01 were comparable with the values observed for canonical length (8 to 11 aa) HLA-A*02:01-restricted peptides. We solved the structures of two 15-mer epitopes in complex with HLA-A*02:01, within which the peptides adopted distinct super-bulged conformations. Moreover, we demonstrate that T-cells can recognize the 15-mer peptides in the context of HLA-A*02:01, indicating that these 15-mer peptides represent immunogenic ligands. Collectively, our data expand our understanding of longer epitopes in the context of HLA-I, highlighting that they are not limited to the HLA-B family, but can bind the ubiquitous HLA-A*02:01 molecule, and play an important role in T-cell immunity.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
Uncontrolled Keywords: Crystallography; Immunology; Mass Spectrometry (MS); Peptide Conformation; Peptides; HLA-A*02:01; Human Leukocyte Antigen Class I; T-cell Immunity; Peptidomics
Publisher: American Society for Biochemistry and Molecular Biology
ISSN: 1083-351X
Last Modified: 07 Feb 2019 11:42

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