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

Citation
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
ISSN journal
00278424 → ACNP
Volume
95
Issue
26
Year of publication
1998
Pages
15571 - 15576
Database
ISI
SICI code
0027-8424(199812)95:26<15571:VAPPCT>2.0.ZU;2-Y
Abstract
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.