Melanoma inhibitor of apoptosis protein (ML-IAP) specific cytotoxic T lymphocytes cross-react with an epitope from the auto-antigen SS56.
A large proportion of melanoma patients host a spontaneous T-cell response specifically against ML-IAP-derived peptides. In this study, we describe that some ML-IAP-specific cytotoxic T cells isolated from melanoma patients cross react with an epitope from the auto-antigen SS56. SS56 is a recently described target of autoantibody responses in Sjögren's syndrome (SS) as well as systemic lupus erythematosus (SLE). Here, we describe that SS56 is also an auto-antigen for T cells in SS and SLE. Hence, SS56-specific T cells could readily be detected in circulation and among the infiltrating cells of SLE skin lesions. SS56-specific T cells were able to lyse target cells presenting the peptide epitope on the surface. Notably, SS56-specific CD8 T cells isolated from an SS patient cross reacted with the ML-IAP epitope. This early evidence of a target for auto-reactive CTL in SS and SLE patients; it is to our knowledge previously unreported and underscores the important role of CD8 T cells in autoimmune disorders. Furthermore, the cross-reactivity against the auto-antigen SS56 and the tumor-antigen ML-IAP confirms the link between autoimmunity and anti-cancer cellular immune responses.
Baek Sørensen
Rikke
R
Center for Cancer Immune Therapy, Department of Haematology, Herlev University Hospital, Herlev, Denmark.
Faurschou
Mikkel
M
Troelsen
Lone
L
Schrama
David
D
Jacobsen
Søren
S
Becker
Jürgen C
JC
Thor Straten
Per
P
Andersen
Mads Hald
MH
D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D003429:Cross Reactions; D000939:Epitopes; D005434:Flow Cytometry; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D009363:Neoplasm Proteins / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D012859:Sjogren's Syndrome / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000276:immunology*
D048868:Adaptor Proteins, Signal Transducing; D001324:Autoantigens; C419866:BIRC7 protein, human; D000939:Epitopes; D051034:Inhibitor of Apoptosis Proteins; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D000070584:Tripartite Motif Proteins; C437970:TRIM68 protein, human; D044767:Ubiquitin-Protein Ligases