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* Center for Molecular Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, People’s Republic of China;
Laboratory of Structural Biology, Tsinghua University, Beijing, People’s Republic of China;
Department of Obstetrics and Gynaecology, Zhujiang Hospital, Nanfang Medical University, Guangzhou, People’s Republic of China;
Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Oxford, Oxfordshire, United Kingdom;
¶ Nuffield Department of Clinical Medicine, University of Oxford, Oxford, Oxfordshire, United Kingdom; and
|| Graduate School, Chinese Academy of Sciences, Beijing, People’s Republic of China
The infection of rhesus macaques (Macaca mulatta) by the SIV is the best animal model for studying HIV infection and for AIDS vaccine development. A prevalent MHC class I allele, Mamu-A*01, is known to correlate with containment of SIV, which has been extensively explored in studies of CTL-based vaccination concepts. We determined the crystal structures of Mamu-A*01 complexed with two immunodominant SIV epitopes: the nonamer CM9 of group-specific Ag (Gag, 181–189; CTPYDINQM) and the octamer TL8 of transcription activator (Tat, 28–35; TTPESANL). The overall structures of the two Mamu-A*01 complexes are similar to other MHC class I molecules. Both structures confirm the presence of an absolutely conserved proline anchor residue in the P3 position of the Ag, bound to a D pocket of the Mamu-A*01 H chain with optimal surface complementarity. Like other MHC/peptide complex structures, the P2 and C-terminal residues of the epitopes are also important for anchoring to the MHC molecule, whereas the middle residues form an arch and their side chains are directed into solvent. These two structures reveal details of how Mamu-A*01 interacts with two well-studied epitopes at the atomic level. We discuss the structural basis of CTL escape, based on molecular models made possible by these two structures. The results we present in this study are most relevant for the rational design of Mamu-A*01-restricted CTL epitopes with improved binding, as a step toward development of AIDS vaccines.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by a grant from Chinese Academy of Sciences Knowledge Innovation Project Grant no. KSCX2-SW-227, a grant from the National Basic Research Program (Project 973) of the Ministry of Science and Technology of the People’s Republic of China (Grant no. 2006CB504204), and grants from National Natural Science Foundation of China (Grant nos. 30440020 and 30671903). G.F.G. is a distinguished young investigator of the Natural Science Foundation of China (Grant no. 30525010).
2 Address correspondence and reprint requests to Dr. George F. Gao, Center for Molecular Immunology, Institute of Microbiology, Chinese Academy of Sciences, 13 Beiyitiao, Zhongguancun, Beijing 100080, People’s Republic of China. E-mail address: gaof{at}im.ac.cn
3 Abbreviations used in this paper: pMHC, peptide and class I MHC molecule complex; 
2m, 2-microglobulin; r.m.s., root-mean-squared.
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