1Q94

Structures of HLA-A*1101 in complex with immunodominant nonamer and decamer HIV-1 epitopes clearly reveal the presence of a middle anchor residue

Summary for 1Q94

• Entry DOI: 10.2210/pdb1q94/pdb
• Related: 1QVO
• Descriptor: HLA class I histocompatibility antigen, A-11 alpha chain, Beta-2-microglobulin, nonamer reverse transcriptase (AIFQSSMTK), ... (4 entities in total)
• Functional Keywords: immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 6
• Total formula weight: 89495.19

Authors

Li, L.,McNicholl, J.M.,Bouvier, M. (deposition date: 2003-08-22, release date: 2004-06-01, Last modification date: 2020-02-05)

Primary citation

Li, L.,Bouvier, M.
Structures of HLA-A*1101 complexed with immunodominant nonamer and decamer HIV-1 epitopes clearly reveal the presence of a middle, secondary anchor residue.
J.Immunol., 172:6175-6184, 2004

PubMed Abstract: HLA-A*1101 is one of the most common human class I alleles worldwide. An increased frequency of HLA-A*1101 has been observed in cohorts of female sex workers from Northern Thailand who are highly exposed to HIV-1 and yet have remained persistently seronegative. In view of this apparent association of HLA-A*1101 with resistance to acquisition of HIV-1 infection, and given the importance of eliciting strong CTL responses to control and eliminate HIV-1, we have determined the crystal structure of HLA-A*1101 complexed with two immunodominant HIV-1 CTL epitopes: the nonamer reverse transcriptase(313-321) (AIFQSSMTK) and decamer Nef(73-82) (QVPLRPMTYK) peptides. The structures confirm the presence of primary anchor residues P2-Ile/-Val and P9-/P10-Lys, and also clearly reveal the presence of secondary anchor residues P6-Ser for reverse transcriptase and P7-Met for Nef. The overall backbone conformation of both peptides is defined as two bulges that are separated by a more buried middle residue. In this study, we discuss how this topology may offer functional advantages in the selection and presentation of HIV-1 CTL epitopes by HLA-A*1101. Overall, this structural analysis permits a more accurate definition of the peptide-binding motif of HLA-A*1101, the characterization of its antigenic surface, and the correlation of molecular determinants with resistance to HIV-1 infection. These studies are relevant for the rational design of HLA-A*1101-restricted CTL epitopes with improved binding and immunological properties for the development of HIV-1 vaccines.

PubMed: 15128805

Experimental method

X-RAY DIFFRACTION (2.4 Å)