8XKE

The structure of HLA-A/14-3-D

Summary for 8XKE

• Entry DOI: 10.2210/pdb8xke/pdb
• Descriptor: HLA class I heavy chain, Beta-2-microglobulin, GLU-VAL-ASP-ASN-ALA-THR-ARG-PHE-ALA-SER-VAL-TYR, ... (4 entities in total)
• Functional Keywords: complex, peptide presentation, immune system, viral protein/immune system, viral protein-immune system complex
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 44888.77

Authors

Zhang, J.N.,Yue, C.,Liu, J.,Sun, Z.Y. (deposition date: 2023-12-23, release date: 2024-07-10, Last modification date: 2024-11-13)

Primary citation

Zhang, J.,Yue, C.,Lin, Y.,Tian, J.,Guo, Y.,Zhang, D.,Guo, Y.,Ye, B.,Chai, Y.,Qi, J.,Zhao, Y.,Gao, G.F.,Sun, Z.,Liu, J.
Uncommon P1 Anchor-featured Viral T Cell Epitope Preference within HLA-A*2601 and HLA-A*0101 Individuals.
Immunohorizons, 8:415-430, 2024

PubMed Abstract: The individual HLA-related susceptibility to emerging viral diseases such as COVID-19 underscores the importance of understanding how HLA polymorphism influences peptide presentation and T cell recognition. Similar to HLA-A*0101, which is one of the earliest identified HLA alleles among the human population, HLA-A*2601 possesses a similar characteristic for the binding peptide and acts as a prevalent allomorph in HLA-I. In this study, we found that, compared with HLA-A*0101, HLA-A*2601 individuals exhibit distinctive features for the T cell responses to SARS-CoV-2 and influenza virus after infection and/or vaccination. The heterogeneous T cell responses can be attributed to the distinct preference of HLA-A*2601 and HLA-A*0101 to T cell epitope motifs with negative-charged residues at the P1 and P3 positions, respectively. Furthermore, we determined the crystal structures of the HLA-A*2601 complexed to four peptides derived from SARS-CoV-2 and human papillomavirus, with one structure of HLA-A*0101 for comparison. The shallow pocket C of HLA-A*2601 results in the promiscuous presentation of peptides with "switchable" bulged conformations because of the secondary anchor in the median portion. Notably, the hydrogen bond network formed between the negative-charged P1 anchors and the HLA-A*2601-specific residues lead to a "closed" conformation and solid placement for the P1 secondary anchor accommodation in pocket A. This insight sheds light on the intricate relationship between HLA I allelic allomorphs, peptide binding, and the immune response and provides valuable implications for understanding disease susceptibility and potential vaccine design.

PubMed: 38885041
DOI: 10.4049/immunohorizons.2400026

Experimental method

X-RAY DIFFRACTION (1.92 Å)