title: Antibody-functionalized peptidic membranes for neutralization of allogeneic skin antigen-presenting cells.
abstract: We report herein application of an in situ material strategy to attenuate allograft T cell responses in a skin transplant mouse model. Functionalized peptidic membranes were used to impede trafficking of donor antigen-presenting cells (dAPCs) from skin allografts in recipient mice. Membranes formed by self-assembling peptides (SAPs) presenting antibodies were found to remain underneath grafted skins for up to 6 days. At the host-graft interface, dAPCs were targeted by using a monoclonal antibody that binds to a class II major histocompatibility complex (MHC) molecule (I-A(d)) expressed exclusively by donor cells. Using a novel cell labeling near-infrared nanoemulsion, we found more dAPCs remained in allografts treated with membranes loaded with anti-I-A(d) antibodies than without. In vitro, dAPCs released from skin explants were found adsorbed preferentially on anti-I-A(d) antibody-loaded membranes. Recipient T cells from these mice produced lower concentrations of interferon-gamma cultured ex vivo with donor cells. Taken together, the data indicate that the strategy has the potential to alter the natural course of rejection immune mechanisms in allogeneic transplant models.
authors.affiliation: Division of Pharmaceutical Sciences, Duquesne University, PA, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wen
authors.affiliation: Department of Radiology, University of Pittsburgh, PA, USA.
authors.forename: Wen
authors.initials: W
authors.lastname: Liu
authors.affiliation: Division of Pharmaceutical Sciences, Duquesne University, PA, USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Bagia
authors.affiliation: Department of Radiology, University of Pittsburgh, PA, USA.
authors.forename: Shaojuan
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Radiology, University of Pittsburgh, PA, USA; Department of Bioengineering, University of Pittsburgh, PA, USA; University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
authors.forename: Mingfeng
authors.initials: M
authors.lastname: Bai
authors.affiliation: Division of Pharmaceutical Sciences, Duquesne University, PA, USA; McGowan Institute of Regenerative Medicine, Pittsburgh, PA, USA.
authors.forename: Jelena M
authors.initials: JM
authors.lastname: Janjic
authors.affiliation: Department of Pathology, University of Pittsburgh, PA, USA; Department of Immunology, University of Pittsburgh, PA, USA.
authors.forename: Nick
authors.initials: N
authors.lastname: Giannoukakis
authors.affiliation: McGowan Institute of Regenerative Medicine, Pittsburgh, PA, USA; Department of Chemistry and Biochemistry, Duquesne University, PA, USA.
authors.forename: Ellen S
authors.initials: ES
authors.lastname: Gawalt
authors.affiliation: Division of Pharmaceutical Sciences, Duquesne University, PA, USA. Electronic address: meng@duq.edu.
authors.forename: Wilson S
authors.initials: WS
authors.lastname: Meng
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology*; D002462:Cell Membrane / Q000378:metabolism; D003199:Computer Systems; D004655:Emulsions / Q000737:chemistry; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D055767:Immobilized Proteins / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis; D008198:Lymph Nodes / Q000166:cytology; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D053758:Nanoparticles / Q000737:chemistry; D009500:Neutralization Tests; D010455:Peptides / Q000737:chemistry / Q000276:immunology*; D012867:Skin / Q000166:cytology*; D016038:Skin Transplantation; D019265:Spectroscopy, Near-Infrared; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous
chemical_list: D000906:Antibodies; D004655:Emulsions; D055767:Immobilized Proteins; D007074:Immunoglobulin G; D010455:Peptides; D007371:Interferon-gamma
keywords: EAK16-II; His-tags; Protein formulation; Self-assembling peptides; Skin allograft