Gene conversion between murine class II major histocompatibility complex loci. Functional and molecular evidence from the bm 12 mutant.
Gene conversion between murine class II major histocompatibility complex loci. Functional and molecular evidence from the bm 12 mutant.
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DOI：
10.1084/jem.160.4.1184
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发表时间：
1984-10-01
期刊：
影响因子：
--
通讯作者：
Fathman CG
中科院分区：
文献类型：
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作者：
Mengle-Gaw L;Conner S;McDevitt HO;Fathman CG
在这项研究中提出的实验定义了bm 12突变的分子基础。同种异体反应性T细胞克隆4.1.4的初始表征显示该克隆识别存在于E β B和A β bm 12链上的同种异体决定簇，但不识别bm 12亲本A β B链上的同种异体决定簇。为了确定I-E β产物和突变体I-A β产物之间共有的序列的程度，我们分离了E β B基因的cDNA克隆并测定了其核苷酸序列。E β B、A β B和A β bm 12的核苷酸序列比较显示，A β bm 12基因与E β B基因在其与A β B亲本不同的区域相同。我们预测bm 12突变是由该区域的基因转换引起的，该区域跨越成熟A β链的氨基酸残基67-71之间的14个核苷酸，从E β B基因座到A β B基因座的相应位置。通过同种异体反应性T细胞克隆识别跨越先前定义的E β等位基因“高变”区之一的该区域提供了这些高变区在T细胞刺激中的功能重要性的第一个直接证据。涉及这些等位基因可变区之一的基因转换事件的鉴定暗示转换是作用于II类β基因以在与外源抗原或T细胞受体相互作用的Ia分子区域中产生序列多样性的机制，蛋白质序列多态性的区域可能是通过其为生物体提供针对更广泛种类的有效免疫反应的能力而选择的外来抗原。
The experiments presented in this study define the molecular basis of the bm 12 mutation. Initial characterization of an alloreactive T cell clone, 4.1.4, showed this clone to recognize an allodeterminant present on the E beta b and A beta bm12 chains, but not on the bm 12 parent A beta b chain. To define the extent of sequence shared between the I-E beta product and the mutant I-A beta product, we isolated a cDNA clone of the E beta b gene and determined its nucleotide sequence. Comparison of the nucleotide sequences of E beta b, A beta b, and A beta bm12 shows the the A beta bm12 gene to be identical to the E beta b gene in the region where it differs from its A beta b parent. We predict that the bm 12 mutation arose by gene conversion of this region, which spans 14 nucleotides between amino acid residues 67-71 of the mature A beta chain, from the E beta b locus to the corresponding position at the A beta b locus. Recognition of this region, which spans one of the previously defined E beta allelic "hypervariable" regions, by an alloreactive T cell clone provides the first direct evidence of the functional importance of these hypervariable regions in T cell stimulation. The identification of a gene conversion event involving one of these allelic variable regions implicates conversion as a mechanism that acts on class II beta genes to create sequence diversity in regions of Ia molecules that interact with foreign antigen or a T cell receptor, regions where protein sequence polymorphism would presumably be selected for by the expanded ability it affords the organism to mount effective immune responses against a wider variety of foreign antigens.