Marti E, Peveri P, Griot-Wenk M, Muntwyler J, Crameri R, Schaller J, Gerber H, Lazary S
Klinik für Nutztiere und Pferde, University of Berne, Switzerland.
Vet Immunol Immunopathol. 1997 Nov;59(3-4):253-70. doi: 10.1016/s0165-2427(97)00096-2.
An equine immunoglobulin E (IgE) heavy-chain cDNA fragment (CH3-CH4, nucleotides 1132 to 1592) was cloned, expressed in Escherichia coli as a fusion protein with a [His]6-tag and purified over a Ni-NTA column. The recombinant protein was used to immunise hens. Testing of the raised egg yolk immunoglobulin G (IgG) in Western-blot and ELISA revealed high titres against the recombinant equine IgE fragment (reqIgEf). The reqIgEf-specific IgG was successfully affinity-purified on an unconventional affinity matrix: the [His]6-tagged recombinant IgE fragment was bound to Ni-NTA agarose and used to adsorb specific immunoglobulins. In Western-blot of ammonium sulphate precipitated horse serum and bronchoalveolar lavage fluid, separated by SDS-PAGE under denaturing-reducing conditions, the raised antibodies reacted with a protein of approximately 80 kDa. A reaction of the reqIgEf-specific IgG was seen with a 190-200 kDa band when the same horse serum or bronchoalveolar fluid (BALF) was separated under non-reducing conditions. These reactions could be inhibited by preincubation of the immune IgG with reqIgEf, while preincubation with horse IgG did not inhibit the reaction. Antibody-affinity chromatography of horse serum with the reqIgEf-specific chicken IgG resulted in an enrichment of the 80 kDa protein in denaturing Western-blot. Determination of the amino acid composition of this protein and comparison with the equine IgE heavy- chain sequence strongly indicates that the 80 kDa band corresponds to the heavy chain of the horse IgE. The reqIgEf-specific chicken IgG was further characterised in an ELISA for the detection of allergen-specific horse IgE. It was demonstrated that heating IgE positive horse sera at 54 degrees C for 10 min drastically diminished the recognition by the reqIgEf-specific chicken IgG. The reaction is inhibitable by preincubation with reqIgEf in a concentration dependent manner. In addition, preincubation with horse IgG, a nonrelevant [His]6-tagged protein or 2% equine colostrum had no influence on the reqIgEf-specific chicken IgG binding characteristic. This antibody recognising horse IgE will be useful for further studies on the pathogenesis of equine allergic diseases.
克隆了马免疫球蛋白E(IgE)重链cDNA片段(CH3-CH4,核苷酸1132至1592),在大肠杆菌中作为与[His]6标签的融合蛋白表达,并通过Ni-NTA柱纯化。重组蛋白用于免疫母鸡。在Western印迹和ELISA中对产生的蛋黄免疫球蛋白G(IgG)进行检测,结果显示针对重组马IgE片段(reqIgEf)的滴度很高。reqIgEf特异性IgG在非常规亲和基质上成功进行了亲和纯化:将带有[His]6标签的重组IgE片段与Ni-NTA琼脂糖结合,并用于吸附特异性免疫球蛋白。在变性还原条件下通过SDS-PAGE分离的硫酸铵沉淀的马血清和支气管肺泡灌洗液的Western印迹中,产生的抗体与一条约80 kDa的蛋白质发生反应。当在非还原条件下分离相同的马血清或支气管肺泡液(BALF)时,reqIgEf特异性IgG与一条190-200 kDa的条带发生反应。这些反应可通过用reqIgEf预孵育免疫IgG来抑制,而用马IgG预孵育则不会抑制反应。用reqIgEf特异性鸡IgG对马血清进行抗体亲和层析,在变性Western印迹中导致80 kDa蛋白质的富集。对该蛋白质的氨基酸组成进行测定并与马IgE重链序列进行比较,强烈表明80 kDa条带对应于马IgE的重链。reqIgEf特异性鸡IgG在用于检测变应原特异性马IgE的ELISA中进一步进行了表征。结果表明,将IgE阳性马血清在54℃加热10分钟会大大降低reqIgEf特异性鸡IgG的识别。该反应可通过用reqIgEf以浓度依赖方式预孵育来抑制。此外,用马IgG、无关的带有[His]6标签的蛋白质或2%马初乳预孵育对reqIgEf特异性鸡IgG的结合特性没有影响。这种识别马IgE的抗体将有助于进一步研究马过敏性疾病的发病机制。