4G9F

Crystal Structure of C12C TCR-HLAB2705-KK10-L6M

Summary for 4G9F

• Entry DOI: 10.2210/pdb4g9f/pdb
• Related: 4G8E 4G8F 4g8g 4g8i 4g9d
• Descriptor: HLA class I histocompatibility antigen, B-27 alpha chain, Beta-2-microglobulin, Gag protein, ... (7 entities in total)
• Functional Keywords: tcr, t cell, hla b*2705, kk10, kk10-l6m, hiv, immune escape, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 5
• Total formula weight: 96266.79

Authors

Gras, S.,Wilmann, P.G.,Rossjohn, J. (deposition date: 2012-07-23, release date: 2013-03-20, Last modification date: 2024-11-27)

Primary citation

Ladell, K.,Hashimoto, M.,Iglesias, M.C.,Wilmann, P.G.,McLaren, J.E.,Gras, S.,Chikata, T.,Kuse, N.,Fastenackels, S.,Gostick, E.,Bridgeman, J.S.,Venturi, V.,Arkoub, Z.A.,Agut, H.,van Bockel, D.J.,Almeida, J.R.,Douek, D.C.,Meyer, L.,Venet, A.,Takiguchi, M.,Rossjohn, J.,Price, D.A.,Appay, V.
A Molecular Basis for the Control of Preimmune Escape Variants by HIV-Specific CD8(+) T Cells.
Immunity, 38:425-436, 2013

PubMed Abstract: The capacity of the immune system to adapt to rapidly evolving viruses is a primary feature of effective immunity, yet its molecular basis is unclear. Here, we investigated protective HIV-1-specific CD8+ T cell responses directed against the immunodominant p24 Gag-derived epitope KK10 (KRWIILGLNK263-272) presented by human leukocyte antigen (HLA)-B∗2705. We found that cross-reactive CD8+ T cell clonotypes were mobilized to counter the rapid emergence of HIV-1 variants that can directly affect T cell receptor (TCR) recognition. These newly recruited clonotypes expressed TCRs that engaged wild-type and mutant KK10 antigens with similar affinities and almost identical docking modes, thereby accounting for their antiviral efficacy in HLA-B∗2705+ individuals. A protective CD8+ T cell repertoire therefore encompasses the capacity to control TCR-accessible mutations, ultimately driving the development of more complex viral escape variants that disrupt antigen presentation.

PubMed: 23521884
DOI: 10.1016/j.immuni.2012.11.021

Experimental method

X-RAY DIFFRACTION (1.9 Å)