Retargeting of regulatory T cells to surface-inducible autoantigen La/SS-B.
The nuclear autoantigen La can be detected on the surface of dying cells. Here we present an assay which enables us to show that La protein is not limited to the surface of dying cells but will be released upon stress-induced cell death. As released La protein tightly binds to the surface of neighboring intact cells we asked the question whether or not La protein could serve as a stress-inducible target e.g. for redirecting of regulatory T cells (Tregs) into damaged tissues to downregulate an immune response. In order to provide first proof of concept we developed a novel fully humanized single-chain bispecific antibody (bsAb) which on the one hand is directed to the La antigen and on the other hand to the CD3 complex of T cells. A cross-linkage of Tregs with La-decorated target cells mediated by this bsAb resulted indeed in the activation of the Tregs in a target-dependent manner. Moreover, such bsAb activated Tregs displayed a potent suppressive capacity and negatively influenced proliferation, expansion and cytokine production of autologous CD4(+) and CD8(+) Teff cells.
Institute of Immunology, Medical Faculty Carl Gustav Carus, Technical University Dresden, Fetscherstr. 74, 01307 Dresden, Germany.
Stefanie
S
Koristka
Marc
M
Cartellieri
Claudia
C
Arndt
Claudia C
CC
Bippes
Anja
A
Feldmann
Irene
I
Michalk
Kristin
K
Wiefel
Slava
S
Stamova
Marc
M
Schmitz
Gerhard
G
Ehninger
Martin
M
Bornhäuser
Michael
M
Bachmann
D016475:3T3 Cells; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000276:immunology; D001324:Autoantigens / Q000235:genetics / Q000276:immunology*; D017252:CD3 Complex / Q000235:genetics / Q000276:immunology*; D016923:Cell Death / Q000187:drug effects / Q000276:immunology; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D007165:Immunosuppression Therapy; D008213:Lymphocyte Activation / Q000187:drug effects; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D020239:Receptor Cross-Talk / Q000276:immunology; D012261:Ribonucleoproteins / Q000235:genetics / Q000276:immunology*; D057127:Single-Chain Antibodies / Q000276:immunology; D013312:Stress, Physiological / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology; D000097585:SS-B Antigen
D061067:Antibodies, Monoclonal, Humanized; D001324:Autoantigens; D017252:CD3 Complex; D008565:Membrane Proteins; D012261:Ribonucleoproteins; D057127:Single-Chain Antibodies; D000097585:SS-B Antigen