Issue 1, 2021

Finding and characterizing a catalytic antibody light chain, H34, capable of degrading the PD-1 molecule

Abstract

Programmed cell death 1 (PD-1) is an immune checkpoint molecule regulating T-cell function. Preventing PD-1 binding to its ligand PD-L1 has emerged as an important tool in immunotherapy. Here, we describe a unique human catalytic antibody light chain, H34, which mediates enzymatic degradation of human PD-1 peptides and recombinant human PD-1 protein and thus functions to prevent the binding of PD-1 with PD-L1. H34 degraded one half of the PD-1 molecules within about 6 h under the experimental conditions. Investigating the acquisition of the catalytic function by H34, which belongs to subgroup I and lacks a Pro95 residue in CDR-3, revealed the importance of this sequence, as a Pro95-reconstituted mutant (H34-Pro95(+)) exhibited very little catalytic activity to cleave PD-1. Interestingly, EDTA inhibited the catalytic activity of H34, which could work as a metallo-protease. Zn2+ or Co2+ ions may work as a cofactor. It is meaningfull that H34 was obtained from the human antibody gene taken from a healthy volunteer, suggesting that we potentially have such unique molecules in our body.

Graphical abstract: Finding and characterizing a catalytic antibody light chain, H34, capable of degrading the PD-1 molecule

Supplementary files

Article information

Article type
Paper
Submitted
25 8月 2020
Accepted
11 11月 2020
First published
10 12月 2020
This article is Open Access
Creative Commons BY-NC license

RSC Chem. Biol., 2021,2, 220-229

Finding and characterizing a catalytic antibody light chain, H34, capable of degrading the PD-1 molecule

E. Hifumi, H. Taguchi, T. Nonaka, T. Harada and T. Uda, RSC Chem. Biol., 2021, 2, 220 DOI: 10.1039/D0CB00155D

This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. You can use material from this article in other publications, without requesting further permission from the RSC, provided that the correct acknowledgement is given and it is not used for commercial purposes.

To request permission to reproduce material from this article in a commercial publication, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party commercial publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements