VH AND VL REGION STRUCTURE OF ANTIBODIES THAT RECOGNIZE THE (NANP)3 DODECAPEPTIDE SEQUENCE IN THE CIRCUMSPOROZOITE PROTEIN OF PLASMODIUM-FALCIPARUM
VH AND VL REGION STRUCTURE OF ANTIBODIES THAT RECOGNIZE THE (NANP)3 DODECAPEPTIDE SEQUENCE IN THE CIRCUMSPOROZOITE PROTEIN OF PLASMODIUM-FALCIPARUM
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DOI：
10.1002/eji.1830201233
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发表时间：
1990-12-01
影响因子：
5.4
通讯作者：
POLLOK, BA
中科院分区：
文献类型：
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作者：
ANKER, R;ZAVALA, F;POLLOK, BA
恶性疟原虫的子孢子形式在其表面上显示环子孢子（CS）蛋白。 该蛋白的中心结构域具有重复的四肽序列Asn-Ala-Asn-Pro（NANP），并且从生活在疟疾流行区的个体获得的> 90%的子孢子特异性抗体识别该重复序列内的表位。 考虑到这种天然存在的抗原的高度重复结构及其免疫优势，我们有兴趣分析与（NANP）3序列结合的抗体的结构多样性。 对产生对十二肽（NANP）3具有结合特异性的抗体的五种杂交瘤进行免疫球蛋白重链和轻链mRNA的分子表征。 这些杂交瘤通过接种完整的恶性疟原虫子孢子在BALB/c小鼠中产生。 序列分析和北方印迹显示，对于重链，三个拟南芥使用属于V（H）IX家族的V（H）元件，两个使用属于V（H）J558家族的V（H）元件。 在轻链中代表四个不同的V-chi亚组。 还利用不同的D和J-chi区段，而四种重链基因重排涉及J（H）4区段。 这些结果表明，多个V（H）-V（L）基因组合可编码对（NANP）3序列的反应性，表明对该免疫显性区域的鼠抗体应答在结构上是异质性的。
The sporozoite form of Plasmodium falciparum displays on its surface the circumsporozoite (CS) protein. The central domain of this protein possesses a reiterated tetrapeptide sequence Asn-Ala-Asn-Pro (NANP), and > 90% of the sporozoite-specific antibodies obtained from individuals living in malaria endemic areas recognize epitopes within this repeat sequence. Considering the highly repetitive structure of this naturally occurring antigen and its immunodominance, we were interested in analyzing the structural diversity of antibodies that bind to the (NANP)3 sequence. Molecular characterization of immunoglobulin heavy and light chain mRNA was performed for five hybridomas that produce antibodies with binding specificity for the dodecapeptide (NANP)3. These hybridomas were produced in BALB/c mice by inoculation with whole P. falciparum sporozoites. Sequence analysis and Northern blotting showed that for heavy chain, three hydridomas used V(H) elements that belong to the V(H)IX family and two to the V(H)J558 family. Four different V-chi subgroups were represented among the light chains. Different D and J-chi segments are also utilized, while four heavy chain gene rearrangements involved the J(H)4 segment. These results indicated that multiple V(H)-V(L) gene combinations can code for reactivity to the (NANP)3 sequence, demonstrating that the murine antibody response to this immunodominant region is structurally heterogeneous.