ガンマデルタT細胞受容体の構造は,非古典的なMHC T22と複合しています
Erin J Adams1, Yueh-Hsiu Chien, K Christopher Garcia
1Department of Microbiology and Immunology, Stanford University School of Medicine, Fairchild D319, 299 Campus Drive, Stanford, CA 94035-5124, USA.
まとめ
MHCクラスIbに結合するガンマデルタT細胞受容体 (TCRs) の構造が明らかになった. この発見は,ガンマデルタTCRの認識を明確にし,アルファベータTCRと大きく異なる.
科学分野:
- 免疫学 免疫学とは
- 構造生物学 構造生物学とは
- 分子生物学は分子生物学である.
背景:
- ガンマデルタTCR,アルファベタTCRを含むT細胞受容体 (TCR) は,抗体とともに,重要な体内再結合抗原受容体である.
- アルファベータTCRと抗体について,リガンド認識の構造的基礎は確立されていますが,ガマデルタTCRについては,まだほとんど定義されていません.
研究 の 目的:
- ガンマデルタT細胞受容体 (TCR) のリガンド認識の構造的基礎を解明する.
- 特定のマウリンガンマデルタTCR (G8) の原子構造を,その同類のMHCクラスIbリガンド (T22) と複合させた.
主な方法:
- X線結晶学を用いて,ネズミのガンマデルタTCR G8がT22リガンドに結合した3.4 Åの解像度構造を決定した.
- 構造分析は,相互作用のインターフェイス,特にガンマデルタTCRの互補性決定領域3 (CDR3) ループに焦点を当てた.
主要な成果:
- この研究では,ネズミのガンマデルタTCR G8の3.4 Åの構造を,そのMHCクラスIbリガンドであるT22.22と複合体として提示しています.
- ガンマデルタTCR G8は,T22を結合するためにデルタ鎖のCDR3ループで主に生殖線でコードされた残基を使用しています.
- 観察された結合方向は,アルファベータTCR/ペプチド-MHC相互作用で通常見られるものと大きく異なります.
結論:
- 構造データは,アルファベータTCRと比較して,ガンマデルタTCRsのリガンド認識の異なるモードを明らかにしています.
- ゲルムラインでコードされた残留物の支配的な使用は,ガンマデルタT細胞における先天性および適応性免疫認識戦略の潜在的な融合を示唆する.
- この研究は,ガンマデルタ型T細胞機能の基礎にある分子機構に関する重要な洞察を提供します.
関連する概念動画
Assembly of Signaling Complexes
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
G Protein-coupled Receptors
G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
Activation and Inactivation of G Proteins
Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high affinity and are together...
Transducer Mechanism: G Protein–Coupled Receptors
G Protein–Coupled Receptors (GPCRs) are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to various stimuli. GPCRs regulate critical physiological pathways and are excellent drug targets for treating diseases such as diabetes, cancer, obesity, depression, or Alzheimer's. Nearly 35% of approved drugs implement their therapeutic effects by selectively interacting with specific GPCRs.
GPCRs are also called heptahelical, 7TM, or...
GPCRs are also called heptahelical, 7TM, or...
Diversity of Antigen Receptors
Antigen receptors are essential components of the immune system crucial in defending the body against foreign invaders. These receptors are present on the surface of B and T cells, enabling them to recognize antigens and mount an appropriate immune response.
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
T Cell Activation and Clonal Selection
T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
Naive T cells that have not yet encountered an antigen express two primary CD...


