3W39

Crystal structure of HLA-B*5201 in complexed with HIV immunodominant epitope (TAFTIPSI)

Summary for 3W39

• Entry DOI: 10.2210/pdb3w39/pdb
• Descriptor: HLA class I histocompatibility antigen, B-52 alpha chain, Beta-2-microglobulin, peptid from Gag-Pol polyprotein (3 entities in total)
• Functional Keywords: class i major histocompatibility complex, mhc, membrane, immune system
• Biological source: Homo sapiens (human); More
• Cellular location: Membrane; Single-pass type I membrane protein: P30490; Secreted: P61769; Matrix protein p17: Virion (Potential). Capsid protein p24: Virion (Potential). Nucleocapsid protein p7: Virion (Potential). Reverse transcriptase/ribonuclease H: Virion (Potential). Integrase: Virion (Potential): P12499
• Total number of polymer chains: 6
• Total formula weight: 89731.51

Authors

Yagita, Y.,Kuse, N.,Kuroki, K.,Gatanaga, H.,Carlson, J.M.,Chikata, T.,Brumme, Z.L.,Murakoshi, H.,Akahoshi, T.,Pfeifer, N.,Mallal, S.,John, M.,Ose, T.,Matsubara, H.,Kanda, R.,Fukunaga, Y.,Honda, K.,Kawashima, Y.,Ariumi, Y.,Oka, S.,Maenaka, K.,Takiguchi, M. (deposition date: 2012-12-13, release date: 2013-02-13, Last modification date: 2024-10-30)

Primary citation

Yagita, Y.,Kuse, N.,Kuroki, K.,Gatanaga, H.,Carlson, J.M.,Chikata, T.,Brumme, Z.L.,Murakoshi, H.,Akahoshi, T.,Pfeifer, N.,Mallal, S.,John, M.,Ose, T.,Matsubara, H.,Kanda, R.,Fukunaga, Y.,Honda, K.,Kawashima, Y.,Ariumi, Y.,Oka, S.,Maenaka, K.,Takiguchi, M.
Distinct HIV-1 Escape Patterns Selected by Cytotoxic T Cells with Identical Epitope Specificity
J.Virol., 87:2253-2263, 2013

PubMed Abstract: Pol283-8-specific, HLA-B*51:01-restricted, cytotoxic T cells (CTLs) play a critical role in the long-term control of HIV-1 infection. However, these CTLs select for the reverse transcriptase (RT) I135X escape mutation, which may be accumulating in circulating HIV-1 sequences. We investigated the selection of the I135X mutation by CTLs specific for the same epitope but restricted by HLA-B*52:01. We found that Pol283-8-specific, HLA-B*52:01-restricted CTLs were elicited predominantly in chronically HIV-1-infected individuals. These CTLs had a strong ability to suppress the replication of wild-type HIV-1, though this ability was weaker than that of HLA-B*51:01-restricted CTLs. The crystal structure of the HLA-B*52:01-Pol283-8 peptide complex provided clear evidence that HLA-B*52:01 presents the peptide similarly to HLA-B*51:01, ensuring the cross-presentation of this epitope by both alleles. Population level analyses revealed a strong association of HLA-B*51:01 with the I135T mutant and a relatively weaker association of HLA-B*52:01 with several I135X mutants in both Japanese and predominantly Caucasian cohorts. An in vitro viral suppression assay revealed that the HLA-B*52:01-restricted CTLs failed to suppress the replication of the I135X mutant viruses, indicating the selection of these mutants by the CTLs. These results suggest that the different pattern of I135X mutant selection may have resulted from the difference between these two CTLs in the ability to suppress HIV-1 replication.

PubMed: 23236061
DOI: 10.1128/JVI.02572-12

Experimental method

X-RAY DIFFRACTION (3.1 Å)