Isolated receptor binding domains of HTLV-1 and HTLV-2 envelopes bind Glut-1 on activated CD4+ and CD8+ T cells

<p>Abstract</p> <p>Background</p> <p>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...

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Main Authors: Montel-Hagen Amélie, Mongellaz Cedric, Lavanya Madakasira, Swainson Louise, Kinet Sandrina, Craveiro Marco, Manel Nicolas, Battini Jean-Luc, Sitbon Marc, Taylor Naomi
Format: Article
Language:English
Published: BMC 2007-05-01
Series:Retrovirology
Online Access:http://www.retrovirology.com/content/4/1/31
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author Montel-Hagen Amélie
Mongellaz Cedric
Lavanya Madakasira
Swainson Louise
Kinet Sandrina
Craveiro Marco
Manel Nicolas
Battini Jean-Luc
Sitbon Marc
Taylor Naomi
author_facet Montel-Hagen Amélie
Mongellaz Cedric
Lavanya Madakasira
Swainson Louise
Kinet Sandrina
Craveiro Marco
Manel Nicolas
Battini Jean-Luc
Sitbon Marc
Taylor Naomi
author_sort Montel-Hagen Amélie
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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 (H1<sub>RBD </sub>or H2<sub>RBD</sub>). 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 H1<sub>RBD </sub>as well as H2<sub>RBD</sub>, 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.</p> <p>Conclusion</p> <p>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.</p>
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spelling doaj.art-7b6c87550eca43b89d13a546dccc225c2022-12-22T01:36:10ZengBMCRetrovirology1742-46902007-05-01413110.1186/1742-4690-4-31Isolated receptor binding domains of HTLV-1 and HTLV-2 envelopes bind Glut-1 on activated CD4+ and CD8+ T cellsMontel-Hagen AmélieMongellaz CedricLavanya MadakasiraSwainson LouiseKinet SandrinaCraveiro MarcoManel NicolasBattini Jean-LucSitbon MarcTaylor Naomi<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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 (H1<sub>RBD </sub>or H2<sub>RBD</sub>). 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 H1<sub>RBD </sub>as well as H2<sub>RBD</sub>, 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.</p> <p>Conclusion</p> <p>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.</p>http://www.retrovirology.com/content/4/1/31
spellingShingle Montel-Hagen Amélie
Mongellaz Cedric
Lavanya Madakasira
Swainson Louise
Kinet Sandrina
Craveiro Marco
Manel Nicolas
Battini Jean-Luc
Sitbon Marc
Taylor Naomi
Isolated receptor binding domains of HTLV-1 and HTLV-2 envelopes bind Glut-1 on activated CD4+ and CD8+ T cells
Retrovirology
title Isolated receptor binding domains of HTLV-1 and HTLV-2 envelopes bind Glut-1 on activated CD4+ and CD8+ T cells
title_full Isolated receptor binding domains of HTLV-1 and HTLV-2 envelopes bind Glut-1 on activated CD4+ and CD8+ T cells
title_fullStr Isolated receptor binding domains of HTLV-1 and HTLV-2 envelopes bind Glut-1 on activated CD4+ and CD8+ T cells
title_full_unstemmed Isolated receptor binding domains of HTLV-1 and HTLV-2 envelopes bind Glut-1 on activated CD4+ and CD8+ T cells
title_short Isolated receptor binding domains of HTLV-1 and HTLV-2 envelopes bind Glut-1 on activated CD4+ and CD8+ T cells
title_sort isolated receptor binding domains of htlv 1 and htlv 2 envelopes bind glut 1 on activated cd4 and cd8 t cells
url http://www.retrovirology.com/content/4/1/31
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