de Villartay J P, Lewis D, Hockett R, Waldmann T A, Korsmeyer S J, Cohen D I
Laboratory of Chemical Biology, National Institute of Diabetes, Digestive, and Kidney Diseases, Bethesda, MD 20892.
Proc Natl Acad Sci U S A. 1987 Dec;84(23):8608-12. doi: 10.1073/pnas.84.23.8608.
The antigen-specific receptor on the surface of mature T lymphocytes is a heterodimer consisting of polypeptides termed alpha and beta. In the course of characterizing human T-cell tumors with an immature (CD4-, CD8-) surface phenotype, we detected a 2-kilobase alpha-related transcript. Analysis of cDNA clones corresponding to this transcript established that a genetic element (which we call TEA, for "T early alpha") located between the alpha-chain variable- and joining-region genes had been spliced to the alpha constant region. The TEA transcript is present early in thymocyte ontogeny, and its expression declines during T-cell maturation. More important, the TEA area functions as an active site for rearrangement within the alpha gene locus. Blot hybridization of restriction enzyme-digested DNA with a TEA probe revealed a narrowly limited pattern of rearrangement in polyclonal thymic DNA, surprisingly different from the pattern expected for the mature alpha gene with its complex diversity. These DNA blots also showed that TEA is generally present in the germ-line configuration in cells expressing the gamma delta heterodimeric receptor and is deleted from mature (alpha beta-expressing) T-lymphocyte tumors and lines. Moreover, the TEA transcript lacked a long open reading frame for protein but instead possessed multiple copies of a repetitive element resembling those utilized in the heavy-chain class switch of the immunoglobulin genes. The temporal nature of the rearrangements and expression detected by TEA suggests that this recombination could mediate a transition between immature (gamma delta-expressing) T cells and mature (alpha beta-expressing) T cells.
成熟T淋巴细胞表面的抗原特异性受体是一种异二聚体，由称为α和β的多肽组成。在对具有未成熟（CD4-、CD8-）表面表型的人类T细胞肿瘤进行特征分析的过程中，我们检测到一个2千碱基的α相关转录本。对与该转录本对应的cDNA克隆进行分析表明，位于α链可变区和连接区基因之间的一个遗传元件（我们称之为TEA，即“T早期α”）已与α恒定区拼接。TEA转录本在胸腺细胞个体发育早期出现，其表达在T细胞成熟过程中下降。更重要的是，TEA区域作为α基因座内重排的活性位点发挥作用。用TEA探针进行的限制性酶切DNA印迹杂交显示，多克隆胸腺DNA中的重排模式非常有限，这与具有复杂多样性的成熟α基因预期的模式惊人地不同。这些DNA印迹还表明，TEA通常以种系构型存在于表达γδ异二聚体受体的细胞中，并从成熟的（表达αβ的）T淋巴细胞肿瘤和细胞系中缺失。此外，TEA转录本缺乏用于蛋白质的长开放阅读框，而是拥有多个类似于免疫球蛋白基因重链类别转换中使用的重复元件的拷贝。TEA检测到的重排和表达的时间特性表明，这种重组可能介导未成熟（表达γδ的）T细胞和成熟（表达αβ的）T细胞之间的转变。
