Increased synapse formation obtained by T cell epitopes containing a CxxC motif in flanking residues convert CD4+ T cells into cytolytic effectors.
The nature of MHC class II-binding epitopes not only determines the specificity of T cell responses, but may also alter effector cell functions. Cytolytic CD4+ T cells have been observed primarily in anti-viral responses, but very little is known about the conditions under which they can be elicited. Their potential as regulators of immune responses, however, deserves investigations. We describe here that inclusion of a thiol-disulfide oxidoreductase motif within flanking residues of class II-restricted epitopes results, both in vitro and in vivo, in elicitation of antigen-specific cytolytic CD4+ T cells through increased synapse formation. We show that both naïve and polarized CD4+ T cells, including Th17 cells, can be converted by cognate recognition of such modified epitopes. Cytolytic CD4+ T cells induce apoptosis on APCs by Fas-FasL interaction. These findings potentially open the way towards a novel form of antigen-specific immunosuppression.
Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium.
Vincent A
VA
Carlier
Luc
L
VanderElst
Wim
W
Janssens
Marc G
MG
Jacquemin
Jean-Marie R
JM
Saint-Remy
D020816:Amino Acid Motifs / Q000235:genetics / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D053222:Fas Ligand Protein / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D054992:Immunological Synapses / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009154:Mutation; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D011490:Protein Disulfide Reductase (Glutathione) / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D019014:fas Receptor / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D018984:Epitopes, T-Lymphocyte; D053222:Fas Ligand Protein; D000949:Histocompatibility Antigens Class II; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D019014:fas Receptor; C445081:myelin oligodendrocyte glycoprotein (35-55); D011490:Protein Disulfide Reductase (Glutathione)