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

SUBMITTER: Hifumi E 

PROVIDER: S-EPMC8341958 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature