title: Human cytomegalovirus inhibits tapasin-dependent peptide loading and optimization of the MHC class I peptide cargo for immune evasion.
abstract: The immune evasion protein US3 of human cytomegalovirus binds to and arrests MHC class I molecules in the endoplasmic reticulum (ER). However, substantial amounts of class I molecules still escape US3-mediated ER retention, suggesting that not all class I alleles are affected equally by US3. Here, we identify tapasin inhibition as the mechanism of MHC retention by US3. US3 directly binds tapasin and inhibits tapasin-dependent peptide loading, thereby preventing the optimization of the peptide repertoire presented by class I molecules. Due to the allelic specificity of tapasin toward class I molecules, US3 affects only class I alleles that are dependent on tapasin for peptide loading and surface expression. Accordingly, tapasin-independent class I alleles selectively escape to the cell surface.
authors.affiliation: College of Life Sciences and Biotechnology, Korea University, 136-701, Seoul, South Korea.
authors.forename: Boyoun
authors.initials: B
authors.lastname: Park
authors.forename: Youngkyun
authors.initials: Y
authors.lastname: Kim
authors.forename: Jinwook
authors.initials: J
authors.lastname: Shin
authors.forename: Sunray
authors.initials: S
authors.lastname: Lee
authors.forename: Kwangmin
authors.initials: K
authors.lastname: Cho
authors.forename: Klaus
authors.initials: K
authors.lastname: Früh
authors.forename: Sungwook
authors.initials: S
authors.lastname: Lee
authors.forename: Kwangseog
authors.initials: K
authors.lastname: Ahn
mesh_terms: D000818:Animals; D017920:Antiporters / Q000378:metabolism*; D003587:Cytomegalovirus; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000378:metabolism*; D006023:Glycoproteins; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism*; D007108:Immune Tolerance / Q000502:physiology*; D007136:Immunoglobulins / Q000378:metabolism*; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D051379:Mice; D010455:Peptides / Q000378:metabolism
chemical_list: D017920:Antiporters; D006023:Glycoproteins; D015395:Histocompatibility Antigens Class I; D017874:Immediate-Early Proteins; D007136:Immunoglobulins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D010455:Peptides; C095111:US3 protein, cytomegalovirus; C107762:tapasin