Kinet Sandrina, Swainson Louise, Lavanya Madakasira, Mongellaz Cedric, Montel-Hagen Amélie, Craveiro Marco, Manel Nicolas, Battini Jean-Luc, Sitbon Marc, Taylor Naomi
Institut de Génétique Moléculaire de Montpellier, Montpellier Cedex 5, France.
Retrovirology. 2007 May 15;4:31. doi: 10.1186/1742-4690-4-31.
We previously identified the glucose transporter Glut-1, a member of the multimembrane-spanning facilitative nutrient transporter family, as a receptor for both HTLV-1 and HTLV-2. However, a recent report concluded that Glut-1 cannot serve as a receptor for HTLV-1 on CD4 T cells: This was based mainly on their inability to detect Glut-1 on this lymphocyte subset using the commercial antibody mAb1418. It was therefore of significant interest to thoroughly assess Glut-1 expression on CD4 and CD8 T cells, and its association with HTLV-1 and -2 envelope binding.
As previously reported, ectopic expression of Glut-1 but not Glut-3 resulted in significantly augmented binding of tagged proteins harboring the receptor binding domains of either HTLV-1 or HTLV-2 envelope glycoproteins (H1RBD or H2RBD). Using antibodies raised against the carboxy-terminal peptide of Glut-1, we found that Glut-1 expression was significantly increased in both CD4 and CD8 cells following TCR stimulation. Corresponding increases in the binding of H1RBD as well as H2RBD, not detected on quiescent T cells, were observed following TCR engagement. Furthermore, increased Glut-1 expression was accompanied by a massive augmentation in glucose uptake in TCR-stimulated CD4 and CD8 lymphocytes. Finally, we determined that the apparent contradictory results obtained by Takenouchi et al were due to their monitoring of Glut-1 with a mAb that does not bind cells expressing endogenous Glut-1, including human erythrocytes that harbor 300,000 copies per cell.
Transfection of Glut-1 directly correlates with the capacities of HTLV-1 and HTLV-2 envelope-derived ligands to bind cells. Moreover, Glut-1 is induced by TCR engagement, resulting in massive increases in glucose uptake and binding of HTLV-1 and -2 envelopes to both CD4 and CD8 T lymphocytes. Therefore, Glut-1 is a primary binding receptor for HTLV-1 and HTLV-2 envelopes on activated CD4 as well as CD8 lymphocytes.
我们之前鉴定出葡萄糖转运蛋白Glut-1，它是跨膜促进性营养物质转运蛋白家族的成员，是人类嗜T淋巴细胞病毒1型（HTLV-1）和人类嗜T淋巴细胞病毒2型（HTLV-2）的受体。然而，最近一份报告得出结论，Glut-1不能作为CD4 T细胞上HTLV-1的受体：这主要是基于他们使用商业抗体mAb1418无法在该淋巴细胞亚群上检测到Glut-1。因此，全面评估Glut-1在CD4和CD8 T细胞上的表达及其与HTLV-1和-2包膜结合的关系具有重要意义。
如先前报道，Glut-1而非Glut-3的异位表达导致携带HTLV-1或HTLV-2包膜糖蛋白（H1RBD或H2RBD）受体结合域的标记蛋白的结合显著增加。使用针对Glut-1羧基末端肽产生的抗体，我们发现TCR刺激后CD4和CD8细胞中Glut-1的表达均显著增加。TCR激活后，观察到静息T细胞上未检测到的H1RBD以及H2RBD的结合相应增加。此外，Glut-1表达的增加伴随着TCR刺激的CD4和CD8淋巴细胞中葡萄糖摄取的大量增加。最后，我们确定竹内等人获得的明显矛盾结果是由于他们用一种不与表达内源性Glut-1的细胞结合的单克隆抗体监测Glut-1，包括每个细胞含有300,000个拷贝的人类红细胞。
Glut-1的转染与HTLV-1和HTLV-2包膜衍生配体结合细胞的能力直接相关。此外，Glut-1由TCR激活诱导，导致葡萄糖摄取以及HTLV-1和-2包膜与CD4和CD8 T淋巴细胞的结合大量增加。因此，Glut-1是活化的CD4以及CD8淋巴细胞上HTLV-1和HTLV-2包膜的主要结合受体。
