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 ORCID: https://orcid.org/0000-0002-2020-7522, 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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Abstract

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:	01 Nov 2022 09:51
URI:	https://orca.cardiff.ac.uk/id/eprint/89433

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