1. ? TLR1-TLR2 TLR1-TLR2L TCR 4-1BB
MyD88
IRAK-4
TRAF1/2
4-1BB
TCR
ZAP70
CD3ζ ? 6 2
cIAP 5 4
TRAF6
IFN-γ production
cIAP
Proliferation
IKKs
MAPKs 1
IκBα
c-Fos
p65
p50
c-Jun
Tlr2 3
4-1bb
AP-1
p65/p50
Supplemental figure 5: Model depicting signaling interaction between T cell receptor, TLR2 and 4-1BB in CD8+ T cells. (1) TCR signals induce the expression of TLR2, TLR1 and 4-1BB. (2) The engagement of TLR1-TLR2 enhances NF-κB expression and MAPK pathways resulting in enhanced 4-1BB expression. (3) TLR stimulation enhances the expression of 4-1BB. (4) 4-1BB signals are necessary for the costimulatory effects of TLR1-TLR2 stimulation on T cell proliferation. (5) Increased cytokine production by TLR stimulation is independent of 4-1BB signals. (6) MyD88 and IRAK-4 are required for the costimulatory effects of 4-1BB signaling through an undefined mechanism.