title: Allelic MHC class I chain related B (MICB) molecules affect the binding to the human cytomegalovirus (HCMV) unique long 16 (UL16) protein: implications for immune surveillance.
abstract: Unique long 16 (UL16) is a viral glycoprotein produced in a host cell infected with human cytomegalovirus (HCMV). It down regulates surface expression of MICB, one of the NKG2D ligands, by forming stable intracellular complexes and retained in the endoplasmic reticulum. Down expression of MICB renders cells less susceptible to NK cell lysis via the NKG2D receptor. Diverse UL16 sequences were identified from different strains of HCMV. MICB is known to be polymorphic. It is not known whether these polymorphisms affect the interactions between these molecules leading to alteration of the immune surveillance of HCMV. The soluble Fc fusion variant UL16 proteins from four laboratory and clinical isolates (AD169, Toledo, PH, and TR) were produced. Four allelic MICB alleles (008, 003, 004, and 00502) were cloned and stable cell lines expressing these MICB alleles were produced. The binding activities of variant UL16 to allelic MICB proteins were determined by flow cytometry. The variants of UL16 proteins did not affect the binding activities to allelic MICB proteins. However, diverse MICB alleles differentially bound UL16. We found that MICB*008 which contains methionine and asparagine at the amino acid positions 98 and 113, respectively, in the alpha 2 domain showed decreased binding activities to UL16 when compared to MICB*003, 004, and MICB*00502 containing isoleucine and aspartic acid, respectively. This finding may imply that MICB*008 is a protective allele and involved in the immune surveillance of HCMV infected patients.
authors.affiliation: Medical Technology PhD Program, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand.
authors.forename: Kanya
authors.initials: K
authors.lastname: Klumkrathok
authors.forename: Amonrat
authors.initials: A
authors.lastname: Jumnainsong
authors.forename: Chanvit
authors.initials: C
authors.lastname: Leelayuwat
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D003586:Cytomegalovirus Infections / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007157:Immunologic Surveillance; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D006023:Glycoproteins; D015395:Histocompatibility Antigens Class I; C098080:MICB antigen; D017361:Viral Nonstructural Proteins