mTECs produce tissue restricted antigens (TRAs)

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Presentation transcript:

mTECs produce tissue restricted antigens (TRAs) Developing T-cells interacts with APCs in the thymus: mTECs produce tissue restricted antigens: SAP CRP Complement C5 α-fetoprotein Albumin Haptoglobin PLP MOG S100β GAD67 GAD65 Somatostatin Trypsin2 Elastase Insulin Α1-Crystallin Retinal S-antigen IRBP Renin Erythropoetin H/K ATPase Tyrosinase Gp100 Lactalbumin Thyroglobulin iFABP Amylase1 PTA MAGE-b1.2.3. - + -/+ DCs cTECS mTECs Klein L et al., Nat Rev Immunol, 2014 Derbinski J et al., Nat Immunol, 2001

Autoimmune regulator (Aire) induce tissue restricted antigen expression Expression pattern of Aire: Expression pattern of tissue restricted antigens: Aire β-Actin cTECs mTECs DCs Macrophages T-cells NTC Klein L et al., Nat Rev Immunol, 2014 Aire is exclusively expressed by mTECs: Aire regulates espression of tissue restricted antigens Aire Derbinski J et al., Nat Immunol, 2001 Anderson MS et al., Science, 2002

Aire-reporter expressing cells and CD4 T-cell immune tolerance Functional experiment: Donors Recipient DO11.10 TCR CD45.2 Foxp3-hCD2 Rag1-/- OVA-specific CD4 T-cell DO11.10 Aire-HCO (CD45.1/CD45.2) Ratio 1:1 Labeling with CFSE Transfer Polyclonal CD4 T-cell CD45.1 Wild type Wild type (CD45.1/CD45.2) CD4+ CD45.2+ Analysis: 0.16 91.1 FCS-W CD45.1 (PB) CD45.2 (PE) 0.11 51.6 CD4 (PE-Cy7) CD45.2 (PE) KJ (APC)

Phenotyping of Aire-reporter positive cells WT Adig Aire-eGFP+ Aire-eGFP+ 0.0 0.4 32.1 Aire (eGFP) Aire (eGFP) SSC CD11c (APC-Cy7) 22.2 28.1 MHC II (PE-Cy7) MHC II (PE-Cy7) CD45 (PerCP-Cy5.5) EpCAM (PE)

Intracellular FACS detection of Aire Phenotype: 0.00 0.03 Aire (AF 488) Thymus MHCII (PE-Cy5) CD11c (APC-Cy7) EpCAM (PE) Aire -/- Aire +/+ 0.00 0.02 Aire (AF 488) Lymph nodes MHCII (PE-Cy5) CD11c (APC-Cy7) EpCAM (PE)