Work

A universal monoallelic human leukocyte antigen class II immunopeptidomic platform for defining the immunogenicity potential of therapeutic proteins

Year: 2025

Type: article

Abstract: An essential criterion for understanding the immunogenicity potential of biotherapeutic proteins is defining the set of peptides processed and presented by human leukocyte antigen (HLA) class II molecules. The heterozygotic state of most individuals and the extreme polymorphic nature of these molecules preclude efforts to define both the precise sequences presented by various alleles and the percentage of patients that are subject to immune responses that can negate clinical benefit and/or result in adverse events. We have developed a diverse, robust, and reproducible monoallelic HLA-DRB1 system in professional antigen presenting cells capable of examining the immunogenic potential of any human IgG. Determination of the allelic restriction of adalimumab CD4 T cell epitopes for two distinct geographic populations underscores the vitality of this system as a central component of a preclinical immunogenicity risk assessment strategy.

Source: Communications Biology

DOI: 10.1038/s42003-025-08692-7