Activation of T lymphocytes is due to their stimulation by presentation of the Ag (carried by the major histocompatibility complex MHC) to the TCR (T cell receptor), but also to a co-stimulation by APC (antigen presenting cell) membrane glycoproteins CD 80 and CD 86. Both act on the T lymphocyte :
- on the CD 28 receptor, which co-activates it
- on the CTLA-4 (cytotoxic lymphocyte associated antigen), which inhibits this activation, but a bit later.
- Abatacept (aimed primarily at Rheumatoid Arthritis), respects the natural structure of CTLA-4.
- Belatacept (aimed essentially at transplantation), has enhanced activity thanks to 2 amino acid substitutions : a leucine by a glutamic acid, an alanine by a tyrosine.
Abatacept and Belatacept block CD 86 and CD 80, but Belatacept blocks them more powerfully, and is especially active in blocking the CD 86 / CD 28 interaction.
