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mTECs produce tissue restricted antigens (TRAs)
Developing T-cells interacts with APCs in the thymus:
Klein L et al., Nat Rev Immunol, 2014
mTECs produce tissue restricted antigens:
DCs cTECS mTECs
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.
+
+
+
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:
Klein L et al., Nat Rev Immunol, 2014
Aire regulates espression of tissue restricted antigens
NTC
Aire
T-cells
Macrophages
DCs
mTECs
cTECs
Aire is exclusively expressed by mTECs:
Aire
β-Actin
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
Aire-HCO
(CD45.1/CD45.2)
DO11.10
Labeling with
CFSE
Ratio 1:1
CD45.1
Transfer
Polyclonal
CD4 T-cell
Wild type
CD45.1 (PB)
FCS-W
CD45.2+
0.16
0.11
CD45.2 (PE)
CD4+
Analysis:
91.1
51.6
CD4 (PE-Cy7)
CD45.2 (PE)
KJ (APC)
Wild type
(CD45.1/CD45.2)
Phenotyping of Aire-reporter positive cells
Adig
0.4
SSC
Aire (eGFP)
Aire (eGFP)
0.0
Aire-eGFP+
Aire-eGFP+
CD11c (APC-Cy7)
WT
32.1
22.2
28.1
MHC II (PE-Cy7)
MHC II (PE-Cy7)
CD45 (PerCP-Cy5.5)
EpCAM (PE)
Intracellular FACS detection of Aire
Aire -/-
Aire +/+
0.03
Aire (AF 488)
Thymus
0.00
Phenotype:
MHCII (PE-Cy5)
Aire -/-
EpCAM (PE)
CD11c (APC-Cy7)
EpCAM (PE)
Aire +/+
0.02
Aire (AF 488)
0.00
Lymph nodes
CD11c (APC-Cy7)
MHCII (PE-Cy5)