Held W, Shakhov A N, Waanders G, Scarpellino L, Luethy R, Kraehenbuhl J P, MacDonald H R, Acha-Orbea H
Ludwig Institute for Cancer Research, Lausanne Branch, Epalinges, Switzerland.
J Exp Med. 1992 Jun 1;175(6):1623-33. doi: 10.1084/jem.175.6.1623.
The classical minor lymphocyte stimulating (Mls) antigens, which induce a strong primary T cell response in vitro, are closely linked to endogenous copies of mouse mammary tumor viruses (MMTV). Expression of Mls genes leads to clonal deletion of T cell subsets expressing specific T cell receptor (TCR) V beta chains. We describe the isolation and characterization of a new exogenous (infectious) MMTV with biological properties similar to the Mls antigen Mls-1a. In vivo administration of either Mls-1a-expressing B cells or the infectious MMTV (SW) led to an increase of T cells expressing V beta 6 followed by their deletion. Surprisingly, different kinetics of deletion were observed with the exogenous virus depending upon the route of infection. Infection through the mucosa led to a slow deletion of V beta 6+ T cells, whereas deletion was rapid after subcutaneous infection. Sequence analysis of the open reading frames in the 3' long terminal repeat of both this exogenous MMTV (SW) and of Mtv-7 (which is closely linked to Mls-1a) revealed striking similarities, particularly in the COOH terminus, which has been implicated in TCR V beta recognition. The identification of an infectious MMTV with the properties of a strong Mls antigen provides a new, powerful tool to study immunity and tolerance in vivo.
经典的小淋巴细胞刺激（Mls）抗原在体外可诱导强烈的初始T细胞反应，它与小鼠乳腺肿瘤病毒（MMTV）的内源性拷贝紧密相连。Mls基因的表达会导致表达特定T细胞受体（TCR）Vβ链的T细胞亚群发生克隆性缺失。我们描述了一种新的外源性（感染性）MMTV的分离和特性，其生物学特性类似于Mls抗原Mls-1a。体内给予表达Mls-1a的B细胞或感染性MMTV（SW）会导致表达Vβ6的T细胞增加，随后这些细胞发生缺失。令人惊讶的是，根据感染途径的不同，外源性病毒会观察到不同的缺失动力学。通过黏膜感染会导致Vβ6 + T细胞缓慢缺失，而皮下感染后缺失则很快。对这种外源性MMTV（SW）和Mtv-7（与Mls-1a紧密相连）的3'长末端重复序列中的开放阅读框进行序列分析，发现了惊人的相似性，特别是在COOH末端，该末端与TCR Vβ识别有关。鉴定出具有强Mls抗原特性的感染性MMTV为研究体内免疫和耐受性提供了一种新的有力工具。
