The FASEB Journal • Research Communication T-Cell inactivation and immunosuppressive activity induced by HIV gp41 via novel interacting motif

ABSTRACT Fusion peptide (FP) of the HIV gp41 molecule inserts into the T cell membrane during virus-cell fusion. FP also blocks the TCR/CD3 interac-tion needed for antigen-triggered T cell activation. Here we used in vitro (fluorescence and immunopre-cipitation), in vivo (T cell mediated autoimmune dis-ease adjuvant arthritis), and in silico methods to identify the FP-TCR novel interaction motif: the!-helical trans-membrane domain (TMD) of the TCR! chain, and the "-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 po-tential target to overcome the immunosuppressant ac-tivity of HIV, and in addition a tool for down-regulating immune mediated inflammation.—Bloch, I., Quintana