AN IMMUNOGLOBULIN HEAVY-CHAIN VARIABLE REGION GENE IS GENERATED FROM 3 SEGMENTS OF DNA - VH, D AND JH
AN IMMUNOGLOBULIN HEAVY-CHAIN VARIABLE REGION GENE IS GENERATED FROM 3 SEGMENTS OF DNA - VH, D AND JH
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DOI：
10.1016/0092-8674(80)90089-6
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发表时间：
1980-01-01
期刊：
影响因子：
64.5
通讯作者：
HOOD, L
中科院分区：
文献类型：
--
作者：
EARLY, P;HUANG, H;HOOD, L
测定了编码小鼠免疫球蛋白[Ig]H链可变区[VH]两部分的不同种系遗传元件的序列。这些元件称为基因片段，是免疫球蛋白L链的V和连接(J)基因片段的H链对应物。VH基因片段编码1-101个氨基酸，JH基因片段编码S107磷酸胆碱结合VH区的107-123个氨基酸。该JH基因片段和另外两个JH基因片段位于5‘-MU之间。恒定区基因(C.mu.)在生殖系DNA中。还测定了与S107密切相关的重排VH基因编码完整的VH区M603的序列。同时测定了S107和M167 H链基因的VH编码序列。将这些序列与胚系基因片段进行比较，表明胚系VH和JH基因片段不包含重排的VH基因中存在的至少13个核苷酸。在S107中，这些核苷酸编码102-106个氨基酸，这些氨基酸构成第三高变区的一部分，从而影响Ig分子的抗原结合特异性。V区的这一部分可能由一个单独的生殖系基因片段编码，该基因片段可以连接到VH和JH片段。这个假定的遗传元件被称为D基因片段，指的是它在H链多样性产生中的作用。基本上相同的非编码序列在VH基因片段的3‘’处被发现，并且作为5“到2个JH基因片段的反向互补。这些都是以前在L V链和J链基因片段附近发现的相同保守核苷酸。每个保守序列由7个和10个保守核苷酸组成，由11个或22个非保守核苷酸的间隔物隔开。高度保守的间距，对应于DNA螺旋的1到2圈，保持了保守核苷酸块之间的精确空间方向。可以相互连接的基因片段(例如VK和JK)总是有不同长度的间隔区。在此基础上，提出了一个由识别L和H链Ig基因片段附近相同保守序列的蛋白质介导的V区基因重排模型。
The sequences of separate germline genetic elements which encode 2 parts of a mouse immunoglobulin [Ig] H chain variable region [VH] were determined. These elements, termed gene segments, are H chain counterparts of the V and joining (J) gene segments of Ig L chains. The VH gene segment encodes amino acids 1-101 and the JH gene segment encodes amino acids 107-123 of the S107 phosphorylcholine-binding VH region. This JH gene segment and 2 other JH gene segments are located 5'' to the .mu. constant region gene (C.mu.) in germline DNA. The sequence of a rearranged VH gene encoding a complete VH region, M603, which is closely related to S107 was also determined. The VH coding sequences of the S107 and M167 H chain mRNA was also determined. Comparison of these sequences to the germline gene segments, suggested that the germline VH and JH gene segments do not contain at least 13 nucleotides which are present in the rearranged VH genes. In S107, these nucleotides encode amino acids 102-106, which form part of the 3rd hypervariable region and consequently influence the antigen-binding specificity of the Ig molecule. This portion of the V region may be encoded by a separate germline gene segment which can be joined to the VH and JH segments. This postulated genetic element was termed the D gene segment, referring to its role in the generation of H chain diversity. Essentially the same noncoding sequences are found 3'' to the VH gene segment and as inverse complements 5'' to 2 JH gene segments. These are the same conserved nucleotides previously found adjacent to L chain V and J gene segments. Each conserved sequence consists of blocks of 7 and 10 conserved nucleotides which are separated by a spacer of either 11 or 22 nonconserved nucleotides. The highly conserved spacing, corresponding to 1 or 2 turns of the DNA helix, maintains precise spatial orientations between blocks of conserved nucleotides. Gene segments which can join to one another (VK and JK, for example) always have spacers of different lengths. Based on these observations, a model is proposed for V region gene rearrangement mediated by proteins which recognize the same conserved sequences adjacent to L and H chain Ig gene segments.