title: Effect of a tapasin mutant on the assembly of the mouse MHC class I molecule H2-K(d).
abstract: Major histocompatibility complex (MHC) class I heavy chain/beta(2)m heterodimers assemble with antigenic peptides through interactions with peptide-loading complex proteins, including tapasin and ERp57. In human cells, a cysteine residue within tapasin (C95) has been shown to form a covalent bond with ERp57. In this study, we focused on the effect of this tapasin amino-acid residue in mouse cells expressing the MHC class I molecule H2-K(d). We showed that a large disulfide-bonded complex was present in the mouse cells that included ERp57, tapasin, and K(d). Furthermore, in mouse cells, unlike human cells, we found that tapasin mutated at C95 can participate in a non-covalent complex with ERp57. Comparison of our findings to earlier findings with a human molecule (HLA-B(*)4402) also revealed that a tapasin C95 mutation has a stronger effect on the maturation and stability of K(d) than HLA-B(*)4402. Overall, our results characterize the influence of this tapasin cysteine residue on the stable surface expression of a mouse MHC class I molecule and reveal differences in tapasin C95 interactions and effects between mouse and human systems.
authors.affiliation: Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Laura C
authors.initials: LC
authors.lastname: Simone
authors.forename: Xiaojian
authors.initials: X
authors.lastname: Wang
authors.forename: Amit
authors.initials: A
authors.lastname: Tuli
authors.forename: Joyce C
authors.initials: JC
authors.lastname: Solheim
mesh_terms: D000818:Animals; D002460:Cell Line; D004220:Disulfides / Q000378:metabolism; D006183:H-2 Antigens / Q000276:immunology*; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D009154:Mutation; D011485:Protein Binding; D019704:Protein Disulfide-Isomerases / Q000378:metabolism
chemical_list: D004220:Disulfides; D006183:H-2 Antigens; D026901:Membrane Transport Proteins; C107762:tapasin; C513195:Pdia3 protein, mouse; D019704:Protein Disulfide-Isomerases
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