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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\u2009\u00c5 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.","bibjson":{"author":[{"initials":"J","lastname":"Liu","name":"Liu J"},{"initials":"KY","lastname":"Chen","name":"Chen KY"},{"initials":"EC","lastname":"Ren","name":"Ren EC"}],"identifier":[{"id":"10.1002/eji.201041370","type":"doi"},{"id":"21538979","type":"pubmed"}],"issue":["7"],"journal":{"iso_abbreviation":"Eur. J. 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