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
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
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DOI：
10.1007/s12275-013-2514-1
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发表时间：
2013-04
影响因子：
3
通讯作者：
K. Klumkrathok;A. Jumnainsong;C. Leelayuwat
中科院分区：
文献类型：
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作者：
K. Klumkrathok;A. Jumnainsong;C. Leelayuwat
独特长16 （UL16）是一种在感染人巨细胞病毒（HCMV）的宿主细胞中产生的病毒糖蛋白。它通过形成稳定的细胞内复合物并保留在内质网中，从而下调NKG2D配体之一MICB的表面表达。MICB的下调表达使细胞通过NKG2D受体对NK细胞裂解的易感性降低。不同HCMV毒株鉴定出不同的UL16序列。众所周知，MICB是多态的。目前尚不清楚这些多态性是否会影响这些分子之间的相互作用，从而导致HCMV免疫监视的改变。从四个实验室和临床分离株（AD169, Toledo， PH和TR）中获得可溶性Fc融合变异体UL16蛋白。克隆了4个MICB等位基因（008、003、004和00502），获得了表达这些MICB等位基因的稳定细胞系。用流式细胞术检测变异UL16与MICB等位基因蛋白的结合活性。UL16蛋白的变异不影响其与MICB等位基因的结合活性。然而，不同的MICB等位基因差异结合UL16。研究发现，与MICB*003、004和MICB*00502相比，MICB*008在α 2结构域的98和113个氨基酸位置分别含有蛋氨酸和天冬氨酸，其对UL16的结合活性降低。这一发现可能暗示MICB*008是一种保护性等位基因，参与了HCMV感染患者的免疫监测。
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.