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恶性疟原虫潜在疫苗抗原中T细胞表位的鉴定。人体淋巴细胞对Pf155/RESA重复和非重复区域反应的研究。

Identification of T epitopes within a potential Plasmodium falciparum vaccine antigen. A study of human lymphocyte responses to repeat and nonrepeat regions of Pf155/RESA.

作者信息

Rzepczyk C M, Ramasamy R, Ho P C, Mutch D A, Anderson K L, Duggleby R G, Doran T J, Murray B J, Irving D O, Woodrow G C, Parkinson D, Brabin B J, Alpers M P

机构信息

Queensland Institute of Medical Research, Brisbane, Australia.

出版信息

J Immunol. 1988 Nov 1;141(9):3197-202.

PMID:2459246
Abstract

PBMC from Melanesians who had high antibody reactivities to fusion proteins encompassing the 3' and the 5' repeat regions of the ring infected E surface antigen (Pf155/RESA), were tested for their ability to respond to synthetic and recombinant peptides representing regions of Pf155/RESA. The aim was to identify T cell epitopes within the Ag. Most of the synthetic peptides from the nonrepeat regions of Pf155/RESA were selected for study on the basis of their tendency to form amphipathic alpha-helices. Peptides representing immunodominant B cell epitopes were also tested. Three-quarters of the Melanesian donors responded to the recombinant peptides (Ag 1505 and Ag 632-100) and to the 8 x 4 mer, a synthetic peptide representative of the 3' repeat region. Whereas all the remaining eight peptides tested elicited a response in at least one donor, three peptides (M40, M42, and BTA3) representing sequences in the nonrepeat regions showed greatest promise as potentially useful T epitopes. Responses in control donors were also observed to most of the peptides but the percentage of responders was lower. T cell bulk lines specific to Ag 1505 and Ag 632-100 were established. All donors were HLA tissue typed, but no obvious correlations between responsiveness and HLA type were observed. Our results suggest that there are T cell epitopes within and outside the repeat regions of Pf155/RESA.

摘要

对来自美拉尼西亚人的外周血单核细胞(PBMC)进行了检测,这些人对包含环状感染红细胞表面抗原(Pf155/RESA)3'和5'重复区域的融合蛋白具有高抗体反应性,检测其对代表Pf155/RESA区域的合成肽和重组肽的反应能力。目的是鉴定该抗原内的T细胞表位。基于Pf155/RESA非重复区域的大多数合成肽形成两亲性α-螺旋的倾向而被选作研究对象。还检测了代表免疫显性B细胞表位的肽。四分之三的美拉尼西亚供体对重组肽(Ag 1505和Ag 632-100)以及对8×4聚体(一种代表3'重复区域的合成肽)有反应。而其余所有测试的8种肽至少在一名供体中引发了反应,代表非重复区域序列的三种肽(M40、M42和BTA3)作为潜在有用的T表位显示出最大的前景。对照供体对大多数肽也有反应,但反应者的百分比更低。建立了针对Ag 1505和Ag 632-100的T细胞大量培养系。对所有供体进行了HLA组织分型,但未观察到反应性与HLA类型之间有明显相关性。我们的结果表明,Pf155/RESA重复区域内外均存在T细胞表位。

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