Affinity and avidity of antibodies to the random polymer (T,G)-A-L and a related ordered synthetic polypeptide

Michal Schwartz, Doron Lancet, Edna Mozes, Michael Sela
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引用次数: 8

Abstract

The affinity values of antibodies to the random synthetic antigen poly-(Tyr,Glu)-poly(dl Ala)-poly(Lys) [known as (T,G)-A-L] and to the ordered (Tyr-Tyr-Glu-Glu)-poly(dlAla)-poly(Lys) [known as (T-T-G-G)-A-L] were measured. Determinations of the association constants were performed by antigen binding capacity assay, ABC, using the whole antigen, and by equilibrium dialysis, using a radioactive conjugate of the ordered peptide T-T-G-G which was found to represent the major determinant of the random (T,G)-A-L. The affinity values of antibodies elicited by high responder mice to (T,G)-A-L and to (T-T-G-G)-A-L were found to be similar. However, a difference of two orders of magnitude was found between the values obtained by the two methods. This difference is partially explained by probability analysis.

Upon immunizing low responder (H-2k) mice with complexes of the antigens with methylated bovine serum albumin (MBSA), an increase in their antibody response was observed. The affinity values of these antibodies were found to be similar to those of high responder antibodies after immunization with either the antigens complexed to MBSA or with the antigens alone. On the basis of these data we conclude that low responder (H-2k) B cells have the potential to produce antibodies of the same specificity and quality as the high responders to the random (T,G)-A-L and to the ordered (T-T-G-G)-A-L, and that the genetic defect in these mice should be located at the level of the B-cell acceptor for the T-cell signal.

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抗体对随机聚合物(T,G) a - l和相关有序合成多肽的亲和力和亲和力
测定抗体对随机合成抗原poly-(Tyr,Glu)-poly(dl Ala)-poly(Lys)[称为(T,G)- a - l]和对有序(Tyr-Tyr-Glu-Glu)-poly(dlAla)-poly(Lys)[称为(T-T-G-G)- a - l]的亲和值。结合常数的测定是通过抗原结合能力测定(ABC)和平衡透析(使用有序肽T-T-G-G的放射性偶联物进行的,该偶联物被发现代表随机(T,G) a - l的主要决定因素。高应答小鼠诱导的抗体对(T,G) a - l和(T-T-G-G) a - l的亲和力值相似。然而,发现两种方法得到的值之间存在两个数量级的差异。这种差异部分可以用概率分析来解释。将抗原与甲基化牛血清白蛋白(MBSA)复合物免疫低应答(H-2k)小鼠后,观察到它们的抗体应答增加。这些抗体在与MBSA复合或单独免疫后的亲和力值与高应答抗体相似。基于这些数据,我们得出结论,低应答(H-2k) B细胞对随机(T,G) a - l和有序(T-T-G-G) a - l具有产生与高应答细胞相同特异性和质量的抗体的潜力,并且这些小鼠的遗传缺陷应该位于T细胞信号的B细胞受体水平。
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