3GSX

Crystal structure of the binary complex between HLA-A2 and HCMV NLV-T8V peptide variant

3GSX の概要

• エントリーDOI: 10.2210/pdb3gsx/pdb
• 関連するPDBエントリー: 3GSN 3GSO 3GSQ 3GSR 3GSU 3GSV 3GSW
• 分子名称: HLA class I histocompatibility antigen, A-2 alpha chain, Beta-2-microglobulin, HCMV pp65 fragment 495-503, variant T8V (NLVPMVAVV), ... (4 entities in total)
• 機能のキーワード: hla, human cytomegalovirus, pp65, t cell receptor (tcr), immune response, public response, immunodominance, restrained response, host-virus interaction, membrane, mhc i, polymorphism, immunoglobulin domain, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Membrane; Single-pass type I membrane protein: P01892; Secreted: P61769
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 44573.68

構造登録者

Reiser, J.-B.,Saulquin, X.,Gras, S.,Debeaupuis, E.,Echasserieau, K.,Kissenpfennig, A.,Legoux, F.,Chouquet, A.,Le Gorrec, M.,Machillot, P.,Neveu, B.,Thielens, N.,Malissen, B.,Bonneville, M.,Housset, D. (登録日: 2009-03-27, 公開日: 2009-08-04, 最終更新日: 2024-10-16)

主引用文献

Gras, S.,Saulquin, X.,Reiser, J.B.,Debeaupuis, E.,Echasserieau, K.,Kissenpfennig, A.,Legoux, F.,Chouquet, A.,Le Gorrec, M.,Machillot, P.,Neveu, B.,Thielens, N.,Malissen, B.,Bonneville, M.,Housset, D.
Structural bases for the affinity-driven selection of a public TCR against a dominant human cytomegalovirus epitope.
J.Immunol., 183:430-437, 2009

PubMed Abstract: Protective T cell responses elicited along chronic human CMV (HCMV) infections are sometimes dominated by CD8 T cell clones bearing highly related or identical public TCR in unrelated individuals. To understand the principles that guide emergence of these public T cell responses, we have performed structural, biophysical, and functional analyses of an immunodominant public TCR (RA14) directed against a major HLA-A*0201-restricted HCMV Ag (pp65(495-503)) and selected in vivo from a diverse repertoire after chronic stimulations. Unlike the two immunodominant public TCRs crystallized so far, which focused on one peptide hotspot, the HCMV-specific RA14 TCR interacts with the full array of available peptide residues. The conservation of some peptide-MHC complex-contacting amino acids by lower-affinity TCRs suggests a shared TCR-peptide-MHC complex docking mode and supports an Ag-driven selection of optimal TCRs. Therefore, the emergence of a public TCR of an oligoclonal Ag-specific response after repeated viral stimulations is based on a receptor displaying a high structural complementarity with the entire peptide and focusing on three peptide hotspots. This highlights key parameters underlying the selection of a protective T cell response against HCMV infection, which remains a major health issue in patients undergoing bone marrow transplantation.

PubMed: 19542454
DOI: 10.4049/jimmunol.0900556

実験手法

X-RAY DIFFRACTION (2.1 Å)