9BL9

KIR3DL1*114 in complex with HLA-A*24:02 presenting the NEF peptide

9BL9 の概要

• エントリーDOI: 10.2210/pdb9bl9/pdb
• 関連するPDBエントリー: 9BL2 9BL3 9BL4 9BL5 9BL6
• 分子名称: MHC class I antigen, Beta-2-microglobulin, NEF peptide, ... (6 entities in total)
• 機能のキーワード: immunoglobulin fold, natural killer cell receptor, kir, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 79039.36

構造登録者

Faoro, C.,Rossjohn, J. (登録日: 2024-04-29, 公開日: 2024-11-13, 最終更新日: 2024-12-11)

主引用文献

Loh, L.,Saunders, P.M.,Faoro, C.,Font-Porterias, N.,Nemat-Gorgani, N.,Harrison, G.F.,Sadeeq, S.,Hensen, L.,Wong, S.C.,Widjaja, J.,Clemens, E.B.,Zhu, S.,Kichula, K.M.,Tao, S.,Zhu, F.,Montero-Martin, G.,Fernandez-Vina, M.,Guethlein, L.A.,Vivian, J.P.,Davies, J.,Mentzer, A.J.,Oppenheimer, S.J.,Pomat, W.,Ioannidis, A.G.,Barberena-Jonas, C.,Moreno-Estrada, A.,Miller, A.,Parham, P.,Rossjohn, J.,Tong, S.Y.C.,Kedzierska, K.,Brooks, A.G.,Norman, P.J.
An archaic HLA class I receptor allele diversifies natural killer cell-driven immunity in First Nations peoples of Oceania.
Cell, 187:7008-, 2024

PubMed Abstract: Genetic variation in host immunity impacts the disproportionate burden of infectious diseases that can be experienced by First Nations peoples. Polymorphic human leukocyte antigen (HLA) class I and killer cell immunoglobulin-like receptors (KIRs) are key regulators of natural killer (NK) cells, which mediate early infection control. How this variation impacts their responses across populations is unclear. We show that HLA-A24:02 became the dominant ligand for inhibitory KIR3DL1 in First Nations peoples across Oceania, through positive natural selection. We identify KIR3DL1114, widespread across and unique to Oceania, as an allele lineage derived from archaic humans. KIR3DL1114NK cells from First Nations Australian donors are inhibited through binding HLA-A24:02. The KIR3DL1114 lineage is defined by phenylalanine at residue 166. Structural and binding studies show phenylalanine 166 forms multiple unique contacts with HLA-peptide complexes, increasing both affinity and specificity. Accordingly, assessing immunogenetic variation and the functional implications for immunity are fundamental toward understanding population-based disease associations.

PubMed: 39476840
DOI: 10.1016/j.cell.2024.10.005

実験手法

X-RAY DIFFRACTION (2.6 Å)