? TLR1-TLR2 TLR1-TLR2L TCR 4-1BB

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? 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.