T-cell presentation of antigen requires cell-to-cell contact for proliferation and anergy induction. Differential MHC requirements for superantigen and autoantigen.
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 [Ca+2]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, alpha HLA-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 II-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.
LaSalle
J M
JM
Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115.
Toneguzzo
F
F
Saadeh
M
M
Golan
D E
DE
Taber
R
R
Hafler
D A
DA
D000938:Antigen-Presenting Cells / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D002450:Cell Communication; D004768:Enterotoxins / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000502:physiology*; D006801:Humans; D007108:Immune Tolerance; D008213:Lymphocyte Activation; D004676:Myelin Basic Protein / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D013211:Staphylococcus aureus / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000942:Antigens, Bacterial; D001324:Autoantigens; D004768:Enterotoxins; D000949:Histocompatibility Antigens Class II; D004676:Myelin Basic Protein; D010446:Peptide Fragments; C031818:enterotoxin B, staphylococcal