Wu T T, Kabat E A
J Exp Med. 1970 Aug 1;132(2):211-50. doi: 10.1084/jem.132.2.211.
In an attempt to account for antibody specificity and complementarity in terms of structure, human kappa-, human lambda-, and mouse kappa-Bence Jones proteins and light chains are considered as a single population and the variable and constant regions are compared using the sequence data available. Statistical criteria are used in evaluating each position in the sequence as to whether it is essentially invariant or group-specific, subgroup-specific, species-specific, etc. Examination of the invariant residues of the variable and constant regions confirms the existence of a large number of invariant glycines, no invariant valine, lysine, and histidine, and only one invariant leucine and alanine in the variable region, as compared with the absence of invariant glycines and presence of three each of invariant alanine, leucine, and valine and two each of invariant lysine and histidine in the constant region. The unique role of glycine in the variable region is emphasized. Hydrophobicity of the invariant residues of the two regions is also evaluated. A parameter termed variability is defined and plotted against the position for the 107 residues of the variable region. Three stretches of unusually high variability are noted at residues 24-34, 50-56, and 89-97; variations in length have been found in the first and third of these. It is hypothesized that positions 24-34 and 89-97 contain the complementarity-determining residues of the light chain-those which make contact with the antigenic determinant. The heavy chain also has been reported to have a similar region of very high variability which would also participate in forming the antibody-combining site. It is postulated that the information for site complementarity is contained in some extrachromosomal DNA such as an episome and is incorporated by insertion into the DNA of the structural genes for the variable region of short linear sequences of nucleotides. The advantages and disadvantages of this hypothesis are discussed.
为了从结构角度解释抗体的特异性和互补性，人κ链、人λ链、小鼠κ链本斯·琼斯蛋白和轻链被视为一个单一群体，并利用现有的序列数据对可变区和恒定区进行比较。使用统计标准来评估序列中的每个位置，判断其是否基本不变或具有组特异性、亚组特异性、物种特异性等。对可变区和恒定区的不变残基进行检查，证实存在大量不变的甘氨酸，不存在不变的缬氨酸、赖氨酸和组氨酸，可变区仅存在一个不变的亮氨酸和丙氨酸；相比之下，恒定区不存在不变的甘氨酸，存在三个不变的丙氨酸、亮氨酸和缬氨酸以及两个不变的赖氨酸和组氨酸。强调了甘氨酸在可变区的独特作用。还评估了两个区域不变残基的疏水性。定义了一个称为变异性的参数，并针对可变区的107个残基的位置进行绘制。在第24 - 34、50 - 56和89 - 97位残基处发现了三段异常高的变异性；在其中第一段和第三段中发现了长度变化。据推测，第24 - 34位和89 - 97位包含轻链的互补决定残基——即与抗原决定簇接触的残基。据报道，重链也有一个类似的非常高变异性的区域，它也会参与形成抗体结合位点。据推测，位点互补的信息包含在一些染色体外DNA中，如附加体，并通过插入可变区结构基因的DNA中由短核苷酸线性序列整合。讨论了这一假设的优缺点。
