T-cell inactivation and immunosuppressive activity induced by HIV gp41 via novel interacting motif

Fusion peptide (FP) of the HIV gp41 molecule inserts into the T cell membrane during virus-cell fusion. FP also blocks the TCR/CD3 interaction needed for antigen-triggered T cell activation. Here we used in vitro (fluorescence and immunoprecipitation), in vivo (T cell mediated autoimmune disease adjuvant arthritis), and in silico methods to identify the FP-TCR novel interaction motif: the α-helical transmembrane domain (TMD) of the TCR α chain, and the β-sheet 5–13 region of the 16 N-terminal aa of FP (FP1–16). Deciphering the molecular mechanism of the immunosuppressive activity of FP provides a new potential target to overcome the immunosuppressant activity of HIV, and in addition a tool for down-regulating immune mediated inflammation.—Bloch, I., Quintana, F. J., Gerger, D., Cohen, T., Cohen, I. R., and Shai, Y. T-Cell inactivation and immunosuppressive activity induced by HIV gp41 via novel interacting motif.