SEQUENCE, SHAPE AND SPECIFICITY OF ANTIBODIES

表征某些抗体特异性的独特型决定簇具有 在抗体研究中被证明有价值的结构和遗传标记 多样性和监管。 A/J株的主要交叉反应独特型 用对偶氮苯胂酸盐免疫的小鼠是可遗传的，由 生殖系基因 我们已经证明（与M。Gefter） 携带这种主要独特型的杂交瘤蛋白在血清学上是 和结构微异质性，但都来源于单一的VH 生殖系基因 此外，还建立了一套不结合胂酸盐的杂交瘤细胞系， 具有这种相同的主要独特型的蛋白质已经由 抗独特型免疫。 结构研究表明， 这些抗独特型抗体与胂酸盐结合密切相关， 具有独特型的抗体，并且来自相同的VH 和vL 生殖系基因 这些分子中抗原结合的丧失已经被证明是一种免疫反应。 与涉及VH 基因和/或H 基因片段 此外，在结合胂酸盐的杂交瘤中， 可能通过体细胞遗传学鉴定出一组丢失了独特型的个体。 V突变H 基因或通过利用不同的D-基因区段 比通常使用的。 从一个结合纵火的Fab片段， 一个带有独特型的杂交瘤已经被结晶化，这使得它很可能 这种独特型的三维结构 知道的 除了主要的独特型，第二个独特型家族 （Id36-60）中的A/J抗偶氮苯胂酸抗体，这是 在结构和血清学上与主要独特型不同， 被定性。 完整的可变区蛋白序列 ID36-60 A/J和BALB/c株的杂交瘤已经被 测定 整个id36-60 家族起源于体细胞突变 单胚系VH 在每个菌株中密切相关的基因。 在 此外，杂交瘤的完整轻链可变区序列 两个菌株的ID36-60 已经确定。 这些 结合链重组研究，研究表明， 在BALB/c品系中由种系基因直接编码的蛋白质是 与抗原的低亲和力相关，表明体细胞 系统中的突变是增强胂酸盐亲和力所必需的。 （AB）

Idiotypic determinants characterizing certain antibody specificities have proven valuable structural and genetic markers in studies of antibody diversity and regulation. The major crossreacting idiotype in strain A/J mice immunized with para-azophenylarsonate is heritable and encoded by germline genes. We have demonstrated (in collaboration with M. Gefter) that hybridoma proteins bearing this predominant idiotype are serologically and structurally microheterogeneous but are all derived from a single VH germline gene. In addition, a set of arsonate-nonbinding hybridoma proteins bearing this same predominant idiotype have been produced by immunization with anti-idiotype. Structural studies have demonstrated that these anti-idiotype antibodies are closely related to the arsonate-binding, idiotype-bearing antibodies and are derived from the same VH and VL germline genes. The loss of antigen binding in these molecules has been correlated with somatic mutation involving either the VH gene and/or JH gene segments. In addition, among arsonate-binding hybridomas it is possible to identify a set that have lost idiotype by virtue of somatic mutation in the VH gene or by utilization of different D-gene segments than are ordinarily utilized. The Fab fragment from an arsonate-binding, idiotype-bearing hybridoma has been crystallized, which makes it likely that the three-dimensional structure responsible for this idiotype will be known. In addition to the predominant idiotype, a second idiotype family (Id36-60) among A/J anti-azophenylarsonate antibodies, which are structurally and serologically distinct from the predominant idiotype, have been characterized. The complete variable region protein sequences of Id36-60 hybridomas for both the A/J and BALB/c strains have been determined. The entire Id36-60 family arises by somatic mutation from single germline VH genes which are closely related in each strain. In addition, the complete light chain variable region sequences of hybridomas from the two strains bearing Id36-60 have been determined. These studies, in combination with chain recombination studies, indicate that the protein encoded directly by the germline gene in the BALB/c strain is associated with low affinity for the antigen, indicating that somatic mutation in the system is necessary to enhance arsonate affinity. (AB)