Variant antigenic peptide promotes cytotoxic T lymphocyte adhesion to target cells without cytotoxicity

摘要: Timelapse video microscopy has been used to record the motility and dynamic interactions between an H-2Db-restricted murine cytotoxic T lymphocyte clone (F5) Db-transfected L929 mouse fibroblasts (LDb) presenting normal or variant antigenic peptides from human influenza nucleoprotein. F5 cells will kill LDb target specific antigen (peptide NP68: ASNENMDAM) after “browsing” their surfaces for 8 min many hours. Cell death is characterized by abrupt cellular rounding followed zeiosis (vigorous “boiling” of cytoplasm blebbing plasma membrane) 10–20 min, with subsequent cessation all activity. Departure lymphocytes unkilled rare, whereas serial killing sometimes observed. In absence peptide, browse much shorter periods, readily leave encounter other targets, while never causing cell death. Two peptides, differing in nonamer position 7 8, also act as antigens, albeit lower efficiency. A third peptide NP34 (ASNENMETM), which differs NP68 both positions yet still binds Db, does not stimulate cytotoxicity. Nevertheless, timelapse analysis shows that leads a significant modification behavior, up-regulating F5–LDb adhesive interactions. These data extend recent studies showing partial agonists may elicit subset responses associated full stimulation, demonstrating TCR interaction antigens can trigger adhesion surface exploration without activating signaling pathway results