title: Mutated HLA-G3 localizes to the cell surface but does not inhibit cytotoxicity of natural killer cells.
abstract: HLA-G plays an important role in the induction of immune tolerance. Various attempts to produce good manufacturing practice levels of HLA-G as a therapeutic molecule have failed to date partly due to the complicated structure of full-length HLA-G1. Truncated HLA-G3 is simpler and easier to produce than HLA-G1 and contains the expected functional epitope in its only α1 monomorphic domain. In this study, we engineered the ER retrieval and retention signal on HLA-G3's cytoplasmic tail by replacing its RKKSSD motif with RAASSD. We observed that mutated HLA-G3 was highly expressed on the cell surface of transduced K562 cells but did not inhibit cytotoxicity of natural killer cells.
authors.affiliation: Escape Therapeutics, Inc., San Jose, CA, United States.
authors.forename: Longmei
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Escape Therapeutics, Inc., San Jose, CA, United States.
authors.forename: Takele
authors.initials: T
authors.lastname: Teklemariam
authors.affiliation: Escape Therapeutics, Inc., San Jose, CA, United States. Electronic address: basil@escapetherapeutics.com.
authors.forename: Basil M
authors.initials: BM
authors.lastname: Hantash
mesh_terms: D020816:Amino Acid Motifs / Q000235:genetics; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D059951:HLA-G Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007108:Immune Tolerance; D016056:Immunodominant Epitopes / Q000235:genetics; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology*; D015202:Protein Engineering; D021382:Protein Sorting Signals / Q000235:genetics; D021381:Protein Transport; D017384:Sequence Deletion / Q000235:genetics; D019076:Transgenes / Q000235:genetics
chemical_list: D059951:HLA-G Antigens; D016056:Immunodominant Epitopes; D021382:Protein Sorting Signals
keywords: Cell surface expression; Cytotoxicity; HLA-G3; Mutation; Natural killer cell