4U6Y

Crystal Structure of HLA-A*0201 in complex with FLNDK, a 15 mer self-peptide

Summary for 4U6Y

• Entry DOI: 10.2210/pdb4u6y/pdb
• Related: 4U6X
• Descriptor: HLA class I histocompatibility antigen, A-2 alpha chain, Beta-2-microglobulin, FLNKD peptide, FLNKDLEVDGHFVTM, ... (6 entities in total)
• Functional Keywords: hla a*0201, ligandome, tcr, t cell, immune system
• Biological source: Homo sapiens (Human); More
• Cellular location: Membrane; Single-pass type I membrane protein: P01892; Secreted . Note=(Microbial infection) In the presence of M: P61769
• Total number of polymer chains: 3
• Total formula weight: 45845.38

Authors

Gras, S.,Chabrol, E.,Rossjohn, J. (deposition date: 2014-07-30, release date: 2014-12-24, Last modification date: 2023-09-27)

Primary citation

Hassan, C.,Chabrol, E.,Jahn, L.,Kester, M.G.,de Ru, A.H.,Drijfhout, J.W.,Rossjohn, J.,Falkenburg, J.H.,Heemskerk, M.H.,Gras, S.,van Veelen, P.A.
Naturally Processed Non-canonical HLA-A*02:01 Presented Peptides.
J.Biol.Chem., 290:2593-2603, 2015

PubMed 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.

PubMed: 25505266
DOI: 10.1074/jbc.M114.607028

Experimental method

X-RAY DIFFRACTION (1.467 Å)