MAP OF SEQUENTIAL B-CELL EPITOPES OF THE HIV-1 TRANSMEMBRANE PROTEIN USING HUMAN-ANTIBODIES AS PROBE

MAP OF SEQUENTIAL B-CELL EPITOPES OF THE HIV-1 TRANSMEMBRANE PROTEIN USING HUMAN-ANTIBODIES AS PROBE
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DOI:
10.1159/000150169
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发表时间:
1990-11-01
期刊:
影响因子:
4.6
通讯作者:
BRASSEUR, R
BRASSEUR, R
中科院分区:
医学4区
文献类型:
--
作者:
GOUDSMIT, J;MELOEN, RH;BRASSEUR, R

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使用感染人类免疫缺陷病毒1型(HIV-1)的个体的抗体,通过抗体反应性肽扫描(Pepscan)来探测41 kD的HIV-1跨膜蛋白(gp 41)的抗原性。11个不同的连续抗体结合位点的定义,通过测试339重叠的九肽跨越完整的gp 41氨基酸序列的反应性。这种分析仅映射长度为9个氨基酸的连续抗体结合位点,并且不鉴定推定的不连续或组装的表位。3个B细胞表位(aa 609-622; aa 655-699; aa 664-681)位于推定的跨膜锚的氨基端边界,2个(aa 732-748; aa 744-762)位于该结构域的羧基端边界,是最具抗原性的。一个抗体结合域(aa 834-852)的4个氨基酸同源的HLA II类β-链的β-1域被识别的血清中的1/4的艾滋病患者测试,而不是任何的8个血清中的无HIV-1的个人。尽管参与病毒复制、细胞病变和可能的免疫抑制的gp 41的功能域被证明与HIV-1感染者的抗体结合,但抗体识别模式与疾病进展之间没有明显的关系。
Antibodies of individuals infected with the human immunodeficiency virus type 1 (HIV-1) were used to probe the antigenicity of the HIV-1 transmembrane protein of 41 kD (gp41) by antibody-reactive peptide scanning (Pepscan). Eleven distinct sequential antibody-binding sites were defined by testing reactivity to 339 overlapping nonapeptides spanning the complete gp41 amino acid sequence. Such analysis only maps continuous antibody-binding sites of nine amino acids in length and does not identify putative discontinuous or assembled epitopes. Three B cell epitopes (aa 609-622; aa 655-699; aa 664-681) at the amino-terminal border of the putative transmembrane anchor and two (aa 732-748; aa 744-762) at the carboxyl-terminal border of this domain were the most antigenic. One antibody-binding domain (aa 834-852) with four amino acids homologous to the beta-1 domain of HLA class II beta-chain was recognized by the serum in 1 of 4 AIDS patients tested and not by any of the eight sera from symptom-free individuals. Although functional domains of gp41 involved in virus replication, cytopathicity and possibly immunossuppression were shown to bind antibodies of HIV-1-infected individuals, no relationship between antibody recognition patterns and disease progression was apparent.