| 论文题目: | Structural basis for the differential classification of HLA-A*6802 and HLA-A*6801 into the A2 and A3 supertypes |
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| 作者: | Niu Ling, Cheng Hao, Zhang Shihong, Tan Shuguang, Zhang Yudan, Qi Jianxun, Liu Jun, George F Gao |
| 联系作者: | Liu Jun, George F Gao |
| 刊物名称: | Molecular immunology |
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| 年份: | 2013 |
| 影响因子: | 3.023 |
| 论文下载: | |
| 摘要: | 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. |
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