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


RESULTS
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.


CONCLUSIONS
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.
Kinet
Sandrina
S
Institut de Génétique Moléculaire de Montpellier, Montpellier Cedex 5, France. kinet@igmm.cnrs.fr
Swainson
Louise
L
Lavanya
Madakasira
M
Mongellaz
Cedric
C
Montel-Hagen
Amélie
A
Craveiro
Marco
M
Manel
Nicolas
N
Battini
Jean-Luc
JL
Sitbon
Marc
M
Taylor
Naomi
N
D000911:Antibodies, Monoclonal / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D002460:Cell Line; D002478:Cells, Cultured; D027342:Excitatory Amino Acid Transporter 2 / Q000096:biosynthesis / Q000378:metabolism*; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D015367:Human T-lymphotropic virus 2 / Q000502:physiology*; D006801:Humans; D008213:Lymphocyte Activation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D011991:Receptors, Virus / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000378:metabolism*; D053585:Virus Attachment
D000911:Antibodies, Monoclonal; D027342:Excitatory Amino Acid Transporter 2; D011948:Receptors, Antigen, T-Cell; D011991:Receptors, Virus; D014759:Viral Envelope Proteins; D005947:Glucose