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T-Cell Presentation of Antigen Requires
Cell-to-Cell Contact for Proliferation and Anergy Induction
Differential MHC Requirements for Superantigen and Autoantigen
The Journal of Immunology,
July 15, 1993, vol. 15 #2, pp. 649-657
Janine M. LaSalle, Frances Toneguzzo, Mark
Saadeh, David E. Golan, Robert Taber, and David A. Hafler
MHC class II+ human T-cell clones are able to
simultaneously present and respond to peptide Ag and superantigen resulting in both
proliferation and subsequent anergy. A major question remains as to whether a single T
cell can present to itself or whether T-T cell interactions are required. We have employed
a novel technique for inhibiting cell-to-cell contact that encapsulates individual T cells
in agarose gel microdrops. Myelin basic protein-reactive individual CD4+ T-cell
clones entrapped within these microdrops neither proliferated nor became anergized to
either peptide Ag or Staphylococcal enterotoxin B (SEB), suggesting that cell-to-cell
contact was required for T-cell presentation of Ag leading to proliferation and anergy.
PMA treatment induced T-cell migration out of gel microdrops, restoring cell-to-cell
contact and resulting in proliferation and anergy after T-cell coculture with peptide or
superantigen. However, analysis of [Ca2+]i release revealed
differences in T-cell responses to SEB versus peptide Ag. The addition of SEB, but not
peptide Ag, induced a calcium flux in solitary T cells. Additionally, aHLA-DR mAb blocked
peptide but not SEB-induced proliferation and anergy induction. Thus, SEB generated an
early signal in solitary T cells that may not be a result of self stimulation via MHC
class II. However, subsequent cell-to-cell contact was required for proliferation and
anergy induction by SEB. These results indicate that peptide Ag requires a MHC class
Il-dependent cell-to-cell interaction for calcium flux, proliferation, and anergy
induction, whereas SEB requires a MHC class II independent cell-to-cell interaction for
proliferation and anergy induction after a TCR-generated calcium flux.
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