Melanoma inhibitor of apoptosis protein (ML-IAP) specific cytotoxic T lymphocytes cross-react with an epitope from the auto-antigen SS56

TY - JOUR

T1 - Melanoma inhibitor of apoptosis protein (ML-IAP) specific cytotoxic T lymphocytes cross-react with an epitope from the auto-antigen SS56

AU - Baek Sørensen, Rikke

AU - Faurschou, Mikkel

AU - Troelsen, Lone

AU - Schrama, David

AU - Jacobsen, Søren

AU - Becker, Jürgen C

AU - Thor Straten, Per

AU - Andersen, Mads Hald

AU - Baek Sørensen, Rikke

AU - Faurschou, Mikkel

AU - Troelsen, Lone

AU - Schrama, David

AU - Jacobsen, Søren

AU - Becker, Jürgen C

AU - Thor Straten, Per

AU - Andersen, Mads Hald

N1 - Keywords: Adaptor Proteins, Signal Transducing; Autoantigens; Cross Reactions; Epitopes; Flow Cytometry; Humans; Inhibitor of Apoptosis Proteins; Lupus Erythematosus, Systemic; Neoplasm Proteins; Peptide Fragments; Receptors, Antigen, T-Cell; Sjogren's Syndrome; T-Lymphocytes, Cytotoxic; Ubiquitin-Protein Ligases

PY - 2009/8/1

Y1 - 2009/8/1

N2 - 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.

AB - 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.

U2 - 10.1038/jid.2009.10

DO - 10.1038/jid.2009.10

M3 - Journal article

C2 - 19212346

SN - 0022-202X

VL - 129

SP - 1992

EP - 1999

JO - Journal of Investigative Dermatology

JF - Journal of Investigative Dermatology

IS - 8

ER -