Dm. Shotton et A. Attaran, Variant antigenic peptide promotes cytotoxic T lymphocyte adhesion to target cells without cytotoxicity, P NAS US, 95(26), 1998, pp. 15571-15576
Citations number
46
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Timelapse video microscopy has been used to record the motility and dynamic
interactions between an H-2D(b)-restricted murine cytotoxic T lymphocyte c
lone (F5) and D-b-transfected L929 mouse fibroblasts (LDb) presenting norma
l or variant antigenic peptides from human influenza nucleoprotein. F5 cell
s will kill LDb target cells presenting specific antigen (peptide NP68: ASN
ENMDAM) after "browsing" their surfaces for between 8 min and many hours. C
ell death is characterized by abrupt cellular rounding followed by zeiosis
(vigorous "boiling" of the cytoplasm and blebbing of the plasma membrane) f
or 10-20 min, with subsequent cessation of all activity. Departure of cytot
oxic T lymphocytes from unkilled target cells is rare, whereas serial killi
ng is sometimes observed. In the absence of antigenic peptide, cytotoxic T
lymphocytes browse target cells for much shorter periods, and readily leave
to encounter other targets, while never causing target cell death. Two var
iant antigenic peptides, differing in nonamer position 7 or 8, also act as
antigens, albeit with lower efficiency. A third variant peptide NP34 (ASNEN
METM), which differs from NP68 in both positions and yet still binds Db, do
es not stimulate F5 cytotoxicity. Nevertheless, timelapse video analysis sh
ows that NP34 leads to a significant modification of cell behavior, by up-r
egulating F5-LDb adhesive interactions. These data extend recent studies sh
owing that partial agonists may elicit a subset of the T cell responses ass
ociated with full antigen stimulation, by demonstrating that TCR interactio
n with variant peptide antigens can trigger target cell adhesion and surfac
e exploration without activating the signaling pathway that results in cyto
toxicity.