Havran W L, Grell S, Duwe G, Kimura J, Wilson A, Kruisbeek A M, O'Brien R L, Born W, Tigelaar R E, Allison J P
Cancer Research Laboratory, University of California, Berkeley 94720.
Proc Natl Acad Sci U S A. 1989 Jun;86(11):4185-9. doi: 10.1073/pnas.86.11.4185.
To study the origin of and the degree of T-cell antigen receptor (TCR) diversity of Thy-1+ dendritic epidermal cells (Thy-1+ dECs) in mice, we have developed a monoclonal antibody (mAb 536) to the gamma delta TCR. mAb 536 binds to and stimulates interleukin 2 secretion from Thy-1+ dEC but not cells that express TCR composed of alpha and beta chains. mAb 536 precipitates CD3-associated gamma and delta chains from lysates of radioiodinated Thy-1+ dECs. Analysis of a panel of hybridomas that express gamma delta TCR indicated that mAb 536 defines an epitope of the variable region (V gamma 3) gene product. Flow cytometric analysis revealed that expression of V gamma 3 in the adult mouse is restricted to cells in the epidermis, where essentially all Thy-1+ cells are V gamma 3+. The majority of CD3+ cells in the 14-day fetal thymus also express V gamma 3. These results indicate that the T-cell complement in epidermis are cells that express gamma delta TCR and that the diversity of antigens recognized by the cells might be restricted by the use of a single V gamma gene segment. Finally, the data raise the intriguing possibility that Thy-1+ dECs may arise from precursors that are among the first to emerge from the developing thymus. This suggests that V gene usage during thymocyte development is highly regulated and has important consequences on the tissue localization and function of the emerging cells. As in other developing tissues, it appears that programmed and transient gene expression determines the fate of the emerging cells.
为了研究小鼠中Thy-1⁺树突状表皮细胞(Thy-1⁺ dECs)的T细胞抗原受体(TCR)多样性的起源和程度,我们开发了一种针对γδ TCR的单克隆抗体(mAb 536)。mAb 536可结合并刺激Thy-1⁺ dEC分泌白细胞介素2,但不能刺激表达由α和β链组成的TCR的细胞。mAb 536能从放射性碘化的Thy-1⁺ dEC裂解物中沉淀出与CD3相关的γ和δ链。对一组表达γδ TCR的杂交瘤的分析表明,mAb 536定义了可变区(Vγ3)基因产物的一个表位。流式细胞术分析显示,成年小鼠中Vγ3的表达仅限于表皮细胞,其中基本上所有Thy-1⁺细胞都是Vγ3⁺。14天胎鼠胸腺中的大多数CD3⁺细胞也表达Vγ3。这些结果表明,表皮中的T细胞成分是表达γδ TCR的细胞,并且这些细胞识别的抗原多样性可能受到单一Vγ基因片段使用的限制。最后,这些数据提出了一个有趣的可能性,即Thy-1⁺ dECs可能起源于最早从发育中的胸腺中出现的前体细胞。这表明胸腺细胞发育过程中的V基因使用受到高度调控,并且对新出现细胞的组织定位和功能具有重要影响。与其他发育中的组织一样,似乎程序性和短暂性基因表达决定了新出现细胞的命运。