Khudyakov Y E, Lopareva E N, Jue D L, Fang S, Spelbring J, Krawczynski K, Margolis H S, Fields H A
Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Public Health Service, U.S. Department of Health and Human Services, Atlanta, Georgia, 30333, USA.
Virology. 1999 Aug 1;260(2):260-72. doi: 10.1006/viro.1999.9813.
Forty-two antigenic domains were identified across the hepatitis A virus (HAV) polyprotein by using a set of 237 overlapping 20-mer synthetic peptides spanning the entire HAV polyprotein and a panel of serum samples from acutely HAV-infected patients. The term "antigenic domain" is used in this study to define a protein region spanned with consecutive overlapping immunoreactive peptides. Nineteen antigenic domains were found within the structural proteins, and 22 were found within the nonstructural proteins, with 1 domain spanning the junction of VP1 and P2A proteins. Five of these domains were considered immunodominant, as judged by both the breadth and the strength of their immunoreactivity. One domain is located within the VP2 protein at position 57-90 aa. A second domain, located at position 767-842 aa, contains the C-terminal part of the VP1 protein and the entire P2A protein. A third domain, located at position 1403-1456 aa, comprises the C-terminal part of the P2C protein and the N-terminal half of the P3A protein. The fourth domain, located at position 1500-1519 aa, includes almost the entire P3B, and the last domain, located at position 1719-1764 aa, contains the C-terminal region of the P3C protein and the N-terminal region of the P3D protein. It is interesting to note that four of the five most immunoreactive domains are derived from small HAV proteins and/or encompass protein cleavage sites separating different HAV proteins. The HAV-specific immunoreactivity of each antigenically reactive peptide was confirmed by using seven HAV seroconversion panels. Collectively, these data demonstrate that HAV structural and nonstructural proteins contain antigenic epitopes that can be efficiently modeled with short synthetic peptides.
通过使用一组覆盖甲型肝炎病毒（HAV）多聚蛋白全长的237个重叠的20肽合成肽以及一组来自急性HAV感染患者的血清样本，在HAV多聚蛋白中鉴定出42个抗原结构域。本研究中使用“抗原结构域”一词来定义由连续重叠的免疫反应性肽段覆盖的蛋白质区域。在结构蛋白中发现了19个抗原结构域，在非结构蛋白中发现了22个，其中1个结构域跨越VP1和P2A蛋白的交界处。根据免疫反应性的广度和强度判断，其中5个结构域被认为是免疫显性的。一个结构域位于VP2蛋白中第57 - 90位氨基酸处。第二个结构域位于第767 - 842位氨基酸处，包含VP1蛋白的C末端部分和整个P2A蛋白。第三个结构域位于第1403 - 1456位氨基酸处，由P2C蛋白的C末端部分和P3A蛋白的N末端一半组成。第四个结构域位于第1500 - 1519位氨基酸处，几乎包含整个P3B，最后一个结构域位于第171,9 - 1764位氨基酸处，包含P3C蛋白的C末端区域和P3D蛋白的N末端区域。值得注意的是，五个免疫反应性最强的结构域中有四个来自HAV小蛋白和/或包含分隔不同HAV蛋白的蛋白切割位点。通过使用七个HAV血清转化样本组证实了每个抗原反应性肽的HAV特异性免疫反应性。总体而言，这些数据表明HAV结构蛋白和非结构蛋白含有可通过短合成肽有效模拟的抗原表位。
