8BP6

Structure of MHC-class I related molecule MR1 with bound M3Ade.

8BP6 の概要

• エントリーDOI: 10.2210/pdb8bp6/pdb
• 分子名称: Beta-2-microglobulin,Major histocompatibility complex class I-related gene protein, (1R,5S)-8-(9H-purin-6-yl)-2-oxa-8-azabicyclo[3.3.1]nona-3,6-diene-4,6-dicarbaldehyde (3 entities in total)
• 機能のキーワード: major histocompatibility complex class i-related gene protein, antigen, immnun system, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 89203.51

構造登録者

Berloffa, G.,Jakob, R.P.,Maier, T. (登録日: 2022-11-16, 公開日: 2023-11-29, 最終更新日: 2026-03-04)

主引用文献

Chancellor, A.,Constantin, D.,Berloffa, G.,Yang, Q.,Nosi, V.,Loureiro, J.P.,Colombo, R.,Jakob, R.P.,Joss, D.,Pfeffer, M.,De Simone, G.,Morabito, A.,Schaefer, V.,Vacchini, A.,Brunelli, L.,Montagna, D.,Heim, M.,Zippelius, A.,Davoli, E.,Haussinger, D.,Maier, T.,Mori, L.,De Libero, G.
The carbonyl nucleobase adduct M 3 Ade is a potent antigen for adaptive polyclonal MR1-restricted T cells.
Immunity, 2024

PubMed Abstract: The major histocompatibility complex (MHC) class I-related molecule MHC-class-I-related protein 1 (MR1) presents metabolites to distinct MR1-restricted T cell subsets, including mucosal-associated invariant T (MAIT) and MR1T cells. However, self-reactive MR1T cells and the nature of recognized antigens remain underexplored. Here, we report a cell endogenous carbonyl adduct of adenine (8-(9H-purin-6-yl)-2-oxa-8-azabicyclo[3.3.1]nona-3,6-diene-4,6-dicarbaldehyde [MAde]) sequestered in the A' pocket of MR1. MAde induced in vitro MR1-mediated stimulation of MR1T cell clones that bound MR1-MAde tetramers. MR1-MAde tetramers identified heterogeneous MR1-reactive T cells ex vivo in healthy donors, individuals with acute myeloid leukemia, and tumor-infiltrating lymphocytes from non-small cell lung adenocarcinoma and hepatocarcinoma. These cells displayed phenotypic, transcriptional, and functional diversity at distinct differentiation stages, indicating their adaptive nature. They were also polyclonal, with some preferential T cell receptor (TCRαβ) pair usage. Thus, MAde is an MR1-presented self-metabolite that enables stimulation and tracking of human-MR1T cells from blood and tissue, aiding our understanding of their roles in health and disease.

PubMed: 39701104
DOI: 10.1016/j.immuni.2024.11.019

実験手法

X-RAY DIFFRACTION (2.8 Å)