Introduction to the use of belatacept: a fusion protein for the prevention of posttransplant kidney rejection

Figures & data

Figure 1 T-cell response to alloantigens.

Notes: The T-cell response to alloantigens requires two different but synergistic signals. Signal 1 is antigen-specific and is delivered via TCR, following recognition of alloantigens coexpressed with an MHC molecule on APCs. Signal 2 is not antigen-specific and is characterized by a link with costimulatory receptor ligand. Signal 3: following these two signals, different pathways are activated. The activation of these transduction pathways leads to the link of IL-2 to its receptor, with activation of mTOR.
Abbreviations: TCR, T-cell receptor; MHC, major histocompatibilty complex; APCs, antigen-presenting cells; mTOR, mammalian target of rapamycin; IL, interleukin; NFAT, nuclear factor of activated T cells.

Figure 2 Costimulatory molecules and biological pathways implicated in the targeting of B7 vs CD28.

Abbreviations: APC, antigen-presenting cell; MHC, major histocompatibilty complex; TCR, T-cell receptor.

Figure 3 Belatacept binds to CD80 (B7-1) and CD86 (B7-2) and blocks costimulation.

Abbreviations: APC, antigen-presenting cell; MHC, major histocompatibilty complex; TCR, T-cell receptor.

Figure 4 Tregs expression.

Notes: Tregs express both the CD4 T-cell receptor and the CD25 IL-2 receptor. Thus, Tregs are CD4+ CD25+. Expression of the Foxp3 is the defining property that determines Tregs development and function. Tregs suppress activation, proliferation, and cytokine production of CD4+ and CD8+ T-cells, and may suppress activity of B-and dendritic cells. Moreover, Tregs can produce and release soluble messengers that have a suppressive function, such as TGF-beta, IL10, and adenosine.
Abbreviations: Tregs, regulatory T-cells; GITR, glucocorticoid-induced TNF receptor; Foxp3, nuclear transcription factor Forkhead box P3; APC, antigen-presenting cell; MHC, major histocompatibilty complex; TCR, T-cell receptor.