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Figure 2 Steps in T Cell Activation
The alloimmune response often requires activation of multiple signaling pathways. The first signal is provided when antigen-presenting cells and antigens activate the T cell receptor. Costimulation (signal 2) occurs when CD80 (B7-1) and CD86 (B7-2) on the antigen-presenting cells engage CD28. Both signals activate important signal transduction pathways (calcineurin, RAS-mitogen-activated protein kinase [MAP-K] pathway, and the nuclear factor-kappa B [NF-kB] pathway). These pathways lead to the expression of many molecules, including interleukin (IL)-2 and IL-15. Interleukin-2 and other cytokines then activate the "target of rapamycin" pathway to provide the trigger for cell proliferation (signal 3). AP-1 = activating protein 1; CDK = cyclins-dependent protein kinase; IKK = serine-threonine protein kinase; JAK3 = Janus kinase 3; MHC = myosin heavy chain; mRNA = messenger ribonucleic acid; mTOR = mammalian target of rapamycin; NFAT = nuclear factor of activated T cells; PKC = protein kinase C; S-1-P = sphingosine-1-phosphate; TCR = T cell receptor. Adapted, with permission, from Halloran (28).
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