CHARACTERIZATION OF HUMAN ANTIBODY-BINDING SITES ON THE EXTERNAL ENVELOPE OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-2
CHARACTERIZATION OF HUMAN ANTIBODY-BINDING SITES ON THE EXTERNAL ENVELOPE OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-2
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DOI：
10.1099/0022-1317-72-6-1261
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发表时间：
1991-06-01
影响因子：
3.8
通讯作者：
GOUDSMIT, J
中科院分区：
文献类型：
--
作者：
DEWOLF, F;MELOEN, RH;GOUDSMIT, J
抗体反应性肽扫描（Pepscan）使用重叠的九肽和人血清作为探针，允许识别的氨基酸显着贡献的抗原-抗体相互作用。合成了502个来自人类免疫缺陷病毒2型株Rod（HIV-2 Rod）外囊膜糖蛋白gp 125的重叠九肽，作为与8个HIV-2感染者血清反应的探针。鉴定了15个抗体结合区，其中2个氨基末端区[E3，氨基酸（aa）118至132; E4，aa 125至141]和4个羧基末端区（E11，aa 303至324; E12，aa 340至358; E14，aa 436至452; E15，aa 486至507）最具抗原性。猴免疫缺陷病毒（SIV），HIV-2和HIV-1之间的结合位点E3和E4的氨基酸高度可变。抗体结合结构域E14和E15在HIV-2毒株中高度保守（HIV-2 Rod与HIV-2 Isy和HIV-2NIHZ的同一性分别为94%和86%）。这两个结构域与SIV（E14为88%，E15为64%）的共同氨基酸多于与HIV-1（E14为41%，E15为45%）的共同氨基酸。流行病学研究显示，非洲HIV-2感染者的血清与E11和E15肽的结合最好（31%，8/26）。非洲HIV-1感染者的血清表现出显着水平的交叉反应的HIV-2肽，特别是E15肽，而欧洲HIV-1感染者的血清仅表现出中等水平的交叉反应。如果使用覆盖E15表位的肽，非洲HIV-2阳性血清对HIV-1和SIV的E15仅显示低水平的交叉反应性（4%）。非洲HIV-1阳性血清与HIV-1 E15肽结合最好（81%，52/64），但与SIV E15（17%，11/64）和HIV-2 E15（25%，16/64）显示出高水平的交叉反应性。欧洲HIV-1阳性血清对HIV-1 E15肽的反应性高（91%，50/55），对HIV-2肽的交叉反应性低（2%，1/55），对SIV E15肽无交叉反应（0/55）。这些结果表明，HIV-2外包膜的免疫显性区域（E11和E15）与HIV-1的免疫显性区域最一致。
Antibody-reactive peptide scanning (Pepscan) using overlapping nonapeptides and human sera as probes allows the identification of amino acids contributing significantly to antigen-antibody interaction. Five-hundred and two overlapping nonapeptides derived from the human immunodeficiency virus type 2 strain Rod (HIV-2Rod) external envelope glycoprotein gp 125 were synthesized to serve as probes for reactivity with eight sera of HIV-2-infected individuals. Fifteen antibody-binding regions were identified, among which two amino-terminal regions [E3, amino acids (aa) 118 to 132; E4, aa 125 to 141] and four carboxy-terminal regions (E11, aa 303 to 324; E12, aa 340 to 358; E14, aa 436 to 452; E15, aa 486 to 507) were the most antigenic. The amino acids in binding sites E3 and E4 were highly variable among simian immunodeficiency virus (SIV), HIV-2 and HIV-1. The antibody-binding domains E14 and E15 were highly conserved among HIV-2 strains (94% and 86% identity of HIV-2Rod to HIV-2Isy and HIV-2NIHZ, respectively). Both domains had more amino acids in common with SIV (88% for E14, 64% for E15) than with HIV-1 (41% for E14, 45% for E15). Epidemiological studies revealed that the sera of African HIV-2-infected individuals bound the E11 and E15 peptides best (31%, 8/26). The sera of African HIV-1-infected individuals showed significant levels of cross-reactivity to the HIV-2 peptides, especially to the E15 peptide, whereas the sera of European HIV-1-infected individuals showed only moderate levels of cross-reactivity. If peptides covering the E15 epitope were used, African HIV-2-positive sera showed only a low level of cross-reactivity (4%) to E15 of HIV-1 and SIV. African HIV-1-positive sera bound the HIV-1 E15 peptide best (81%, 52/64), but showed high levels of cross-reactivity to SIV E15 (17%, 11/64) and HIV-2 E15 (25%, 16/64). European HIV-1-positive sera showed a high level of reactivity to HIV-1 E15 (91%, 50/55) and a low level of cross-reactivity to the HIV-2 (2%, 1/55), and none to the SIV E15 (0/55) peptide. These results indicate that the immunodominant regions of the HIV-2 external envelope (E11 and E15) align with the most immunodominant regions of HIV-1.