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 (FP 1–16 ). 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. FASEB J. 21, 393–401 (2007)