Figure 4.

Mechanism of action of abatacept in LRBA deficiency. (A) normal immune responses are based on a balance between stimulatory signals (interaction of CD28 on T lymphocytes with CD80 and CD86 on antigen presenting cells) and inhibitory signals (block of CD80 and CD86 by CTLA4 expressed by lymphocytes). This balance is particularly critical in regulatory T cells, which can express higher levels of CTLA4. (B) biallelic mutations in LRBA result in impaired recycling of CTLA4 to the membrane, leading to reduced expression of the protein and increased lymphocyte stimulation. The addition of abatacept (CTLA4-Ig) partially compensates the lack of cell-bound CTLA4. T, T cell; APC, Antigen Presenting Cell.