LAUSR

Combinatorial protein engineering methodologies such as phage display are powerful tools for high-throughput investigations of protein-protein interactions. Since originally developed [1], phage display has become a work horse around the world both for basic protein chemistry work as well as for academic and pharmaceutical development of biotherapeutic drugs, e.g. the therapeutic antibodies used in autoimmune disease and cancer. In the current study by Rom an-Mel endez et al [2], the scope has been to use phage display technology to help define the breadth of anti-citrullinated peptide autoantibodies (ACPA) in rheumatoid arthritis (RA). Within the field of clinical immunology, a positive serological antibody test is often part of the clinical diagnostic criteria, and in many disease settings the precise target(s) of autoantibodies are well understood. However, in RA synthetic peptide(s) (CCP2/3) are used in the clinical assays serving as a proxy for ACPA reactivity. The autoantigens contain the modified amino acid citrulline, which is naturally generated by enzymatic modification by PADs, but the precise autoantibody targets are still debated in RA. Phage display has proven an effective method for epitope mapping of monoclonal antibodies as well as for understanding natural immune responses. The phage systems enable screening of a large number of candidate epitopes with more affinity discrimination than peptide arrays, but comes with the caveats of primarily binding to linear epitopes and not including mammalian specific post-translational modifications (PTMs). While randomized peptide libraries have been successfully used in many studies including recently for mapping SARS-CoV2 antibodies [3], cDNA or synthetic peptidome libraries have the advantage of only containing naturally occurring epitopes making them more applicable for directed human serological studies. Many original phage display platforms have used the M13 bacteriophage, yet the T7 phage-based systems have recently shown to be highly competitive, in particular for fast high-