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Updated: Aug 24, 2026

Targeted Antibody Blocking by a Dual-Functional Conjugate of Antigenic Peptide and Fc-III Mimetics (DCAF)
Published on: September 17, 2019
Modulation of FcgammaRI (CD64) ligand binding by blocking peptides of periplakin
Jeffrey M Beekman1, Jantine E Bakema, Joke van der Linden
1Immunotherapy Laboratory, Department of Immunology, University Medical Center Utrecht, Lundlaan 6, 3584 EA, The Netherlands.
Abstract:
FcgammaRI requires both the intracellular domain of the alpha-chain and associated leukocyte Fc receptor (FcR) gamma-chains for its biological function. We recently found the C terminus of periplakin to selectively interact with the cytoplasmic domain of the FcgammaRI alpha-chain. It thereby enhances the capacity of FcgammaRI to bind, internalize, and present antigens on MHC class II. Here, we characterized the domains involved in FcgammaRI-periplakin interaction using truncated and alanine-substituted FcgammaRI mutants and randomly mutagenized periplakin. This allowed us to design TAT peptides that selectively interfered with endogenous FcgammaRI-periplakin interactions. The addition of these peptides to FcgammaRI-expressing cells modulated FcgammaRI ligand binding, as assessed by erythrocyte-antibody-rosetting. These data support a dominant-negative role of C-terminal periplakin for FcgammaRI biological activity and implicate periplakin as a novel regulator of FcgammaRI in immune cells.
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