Transmembrane Domain-Driven Pd-1 Dimers Mediate T Cell Inhibition

Authors

• Elliot A Philips
• Jia Liu
• Audun Kvalvaag
• Alexander M Mørch
• Anna S Tocheva
• Charles Ng
• Hong Liang
• Ian M Ahearn
• Ruimin Pan
• Christina C Luo
• Alexander Leithner
• Zhihua Qin
• Yong Zhou
• Antonio Garcia-España
• Adam Mor
• Dan R Littman
• Michael L Dustin
• Jun Wang
• Xiang-Peng Kong

Language

English

Publication Date

3-8-2024

Journal

Science Immunology

DOI

10.1126/sciimmunol.ade6256

PMID

38457513

PMCID

PMC11166110

PubMedCentral® Posted Date

6-11-2024

PubMedCentral® Full Text Version

Author MSS

Abstract

Programmed cell death-1 (PD-1) is a potent immune checkpoint receptor on T lymphocytes. Upon engagement by its ligands, PD-L1 or PD-L2, PD-1 inhibits T cell activation and can promote immune tolerance. Antagonism of PD-1 signaling has proven effective in cancer immunotherapy, and conversely, agonists of the receptor may have a role in treating autoimmune disease. Some immune receptors function as dimers, but PD-1 has been considered monomeric. Here, we show that PD-1 and its ligands form dimers as a consequence of transmembrane domain interactions and that propensity for dimerization correlates with the ability of PD-1 to inhibit immune responses, antitumor immunity, cytotoxic T cell function, and autoimmune tissue destruction. These observations contribute to our understanding of the PD-1 axis and how it can potentially be manipulated for improved treatment of cancer and autoimmune diseases.

Keywords

Humans, Programmed Cell Death 1 Receptor, Neoplasms, Immune Tolerance, Lymphocyte Activation, Protein Domains, Autoimmune Diseases

Published Open-Access

yes

Recommended Citation

Philips, Elliot A; Liu, Jia; Kvalvaag, Audun; et al., "Transmembrane Domain-Driven Pd-1 Dimers Mediate T Cell Inhibition" (2024). Faculty, Staff and Student Publications. 4289.
https://digitalcommons.library.tmc.edu/uthmed_docs/4289