title: Structural basis for the differential classification of HLA-A*6802 and HLA-A*6801 into the A2 and A3 supertypes.
abstract: High polymorphism is one of the most important features of human leukocyte antigen (HLA) alleles, which were initially classified by serotyping but have recently been re-grouped into supertypes according to their peptide presentation properties. Two relatively prevalent HLA alleles HLA-A*6801 and HLA-A*6802, are classified into the same serotype HLA-A68. However, based on their distinct peptide-binding characteristics, HLA-A*6801 is grouped into A3 supertype, whereas HLA-A*6802 belongs to A2 supertype, similar to HLA-A*0201. Thusfar, the structural basis of the different supertype definitions of these serotyping-identical HLA alleles remains largely unknown. Herein, we determined the structures of HLA-A*6801 and HLA-A*6802 presenting three typical A3 and A2 supertype-restricted peptides, respectively. The binding capabilities of these peptides to HLA-A*6801, HLA-A*6802, and HLA-A*0201 were analyzed. These data indicate that the similar conformations of the residues within the F pocket contribute to close-related peptide binding features of HLA-A*6802 and HLA-A*0201. However, the overall structure and the peptide conformation of HLA-A*6802 are more similar to HLA-A*6801 rather than HLA-A*0201 which illuminates the similar serotype grouping of HLA-A*6802 and HLA-A*6801. Our findings are helpful for understanding the divergent peptide presentation and virus-specific CTL responses impacted by MHC micropolymorphisms and also elucidate the molecular basis of HLA supertype definitions.
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Niu
authors.forename: Hao
authors.initials: H
authors.lastname: Cheng
authors.forename: Shihong
authors.initials: S
authors.lastname: Zhang
authors.forename: Shuguang
authors.initials: S
authors.lastname: Tan
authors.forename: Yudan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jianxun
authors.initials: J
authors.lastname: Qi
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: George F
authors.initials: GF
authors.lastname: Gao
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology; D018360:Crystallography, X-Ray; D015234:HLA-A Antigens / Q000737:chemistry* / Q000145:classification* / Q000235:genetics; D015789:HLA-A2 Antigen / Q000737:chemistry / Q000145:classification / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D012703:Serotyping
chemical_list: D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; C053029:HLA-A*68 antigen; D015789:HLA-A2 Antigen