von Boehmer H, Bonneville M, Ishida I, Ryser S, Lincoln G, Smith R T, Kishi H, Scott B, Kisielow P, Tonegawa S
Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge 02139.
Proc Natl Acad Sci U S A. 1988 Dec;85(24):9729-32. doi: 10.1073/pnas.85.24.9729.
beta transgenic mice have a T-cell receptor beta-chain gene that is prematurely expressed on the surface of CD4- CD8- thymocytes and paired with an uncharacterized non-T-cell receptor alpha-chain polypeptide. The rearrangement of the T-cell receptor variable region gamma chain gene segment V gamma 4, a component of the gamma-chain gene that is rearranged and expressed preferentially on thymocytes of normal adult mice, is severely repressed in beta transgenic mice. Consequently no gamma delta T-cell receptor heterodimers are detectable on the surface of adult thymocytes or splenic T cells. These results indicate that cells expressing alpha beta or gamma (V gamma 4)-delta TCRs originate from a common precursor in which the first productive rearrangement of either the beta or gamma locus determines the further differentiation pathway into either alpha beta or gamma delta T cells. The repression of V gamma 4 rearrangement by a preexisting beta-chain gene may be indicative of one of several mechanisms which ensure that gamma delta and alpha beta receptors do not as a rule appear on the surface of the same cell.
β转基因小鼠具有一个T细胞受体β链基因,该基因在CD4 - CD8 - 胸腺细胞表面过早表达,并与一种未鉴定的非T细胞受体α链多肽配对。T细胞受体可变区γ链基因片段Vγ4是γ链基因的一个组成部分,在正常成年小鼠的胸腺细胞上优先重排和表达,其在β转基因小鼠中受到严重抑制。因此,在成年胸腺细胞或脾T细胞表面未检测到γδT细胞受体异二聚体。这些结果表明,表达αβ或γ(Vγ4)-δTCR的细胞起源于一个共同的前体,其中β或γ基因座的首次有效重排决定了进一步分化为αβ或γδT细胞的途径。预先存在的β链基因对Vγ4重排的抑制可能是确保γδ和αβ受体通常不会出现在同一细胞表面的几种机制之一。