{'fraction_non_alphanumeric': 0.03612903225806452, 'fraction_numerical': 0.03935483870967742, 'mean_word_length': 5.924107142857143, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 3, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Structural insights into the binding of hepatitis B virus core peptide to HLA‐A2 alleles: Towards designing better vaccines

Binding of specific antigenic peptides with human leukocyte antigen (HLA) molecules is a prerequisite for the initiation of T‐cell responses and structural information about the peptide–HLA complex is essential for the detailed understanding of such interactions. HLA‐A2 is the most prevalent HLA allele globally but aside from A*02:01 there is a significant lack of crystal structures, particularly for alleles that occur in high frequencies among Asian populations. Here, we report three HLA‐A2 structures with the immunodominant hepatitis B core antigen 18–27 (HBcAg18–27) epitope, namely A*02:03, A*02:06, and A*02:07 at resolutions of 2.16, 1.70, and 1.75 Å respectively. This comparative analysis reveals that minor polymorphic residue changes between different HLA alleles can induce significant alterations in the major histocompatibility complex–peptide interface, and introduce conformational changes in the p3–p8 peptide region. Circular dichroism analysis demonstrated the HLA‐A2–peptide complexes to have a hierarchy of thermostability and binding affinity in the order of A*02:06>A*02:07>A*02:01>A*02:03. Our findings provide structural insights into the varied HLA‐A2 allele binding of the hepatitis B core antigen 18–27 epitope and the data suggest that chemical modifications of the peptide side chains could be a promising strategy to modulate and improve HLA‐A2–peptide binding affinity for vaccine design.