8ZO4

Crystal structure of Tfh TCR ectodomain thermostable mutant

This is a non-PDB format compatible entry.

Summary for 8ZO4

• Entry DOI: 10.2210/pdb8zo4/pdb
• Descriptor: TCR stable mutant Alpha chain, TCR stable mutant Beta chian, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: t cell receptor, ecotodomain, thermostable mutant, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 4
• Total formula weight: 111543.39

Authors

Mori, S.,Nagae, M.,Yamasaki, S. (deposition date: 2024-05-28, release date: 2025-01-01, Last modification date: 2025-03-26)

Primary citation

Sakai, Y.,Asa, M.,Hirose, M.,Kusuhara, W.,Fujiwara, N.,Tamashima, H.,Ikazaki, T.,Oka, S.,Kuraba, K.,Tanaka, K.,Yoshiyama, T.,Nagae, M.,Hoshino, Y.,Motooka, D.,Van Rhijn, I.,Lu, X.,Ishikawa, E.,Moody, D.B.,Kato, T.,Inuki, S.,Hirai, G.,Yamasaki, S.
A conserved human CD4+ T cell subset recognizing the mycobacterial adjuvant, trehalose monomycolate.
J.Clin.Invest., 135:-, 2024

PubMed Abstract: Mycobacterium tuberculosis causes human tuberculosis (TB). As mycobacteria are protected by a thick lipid cell wall, humans have developed immune responses against diverse mycobacterial lipids. Most of these immunostimulatory lipids are known as adjuvants acting through innate immune receptors, such as C-type lectin receptors. Although a few mycobacterial lipid antigens activate unconventional T cells, the antigenicity of most adjuvantic lipids is unknown. Here, we identified that trehalose monomycolate (TMM), an abundant mycobacterial adjuvant, activated human T cells bearing a unique αβ T cell receptor (αβTCR). This recognition was restricted by CD1b, a monomorphic antigen-presenting molecule conserved in primates but not mice. Single-cell TCR-RNA-Seq using newly established CD1b-TMM tetramers revealed that TMM-specific T cells were present as CD4+ effector memory T cells in the periphery of uninfected donors but expressed IFN-γ, TNF, and anti-mycobacterial effectors upon TMM stimulation. TMM-specific T cells were detected in cord blood and PBMCs of donors without bacillus Calmette-Guérin vaccination but were expanded in patients with active TB. A cryo-electron microscopy study of CD1b-TMM-TCR complexes revealed unique antigen recognition by conserved features of TCRs, positively charged CDR3α, and long CDR3β regions. These results indicate that humans have a commonly shared and preformed CD4+ T cell subset recognizing a typical mycobacterial adjuvant as an antigen. Furthermore, the dual role of TMM justifies reconsideration of the mechanism of action of adjuvants.

PubMed: 39718834
DOI: 10.1172/JCI185443

Experimental method

X-RAY DIFFRACTION (2.6 Å)