Reviewer: S. Randhawa, M.D., Allergist/Immunologist and Assistant Professor at LSU (Shreveport) Department of Allergy and Immunology
There is no T cell response without costimulation. If T cells recognize the antigen but are not co-stimulated, they go in a state of anergy or nonresponsiveness.
Two co-stimulators produce negative response instead of positive response (activation). The negative co-stimulators are CTLA-4 and PD-1 on T cells. They are connected to ITIMs.
Pairs of co-stimulators and their ligands:
Left - antigen presenting cells (APC) -- right - T cells
CD 80 (B7-1 in mouse) -- CD 28
CD 86 (B7-2 in mouse) -- CTLA-4 (negative response)
ICOS-L -- ICOS (class switch)
OX40L -- OX40
CD40 -- CD40L (class switch)
PD-L1/PD-L2 -- PD-1 (negative response, PD - Programmed Death)
Abbreviations: ITIM, immunoreceptor tyrosine inhibitory motifs; ICOS, inducible co-stimulator; PD-1, programmed death.
CD152 is cytotoxic T-lymphocyte antigen-4 (CTLA-4). CTLA-4 binds to CD80 and CD86 receptors with a higher affinity than CD28, and inhibits T cell activation.
Abatacept (Orencia) is CTLA4-human IgG1 fusion protein against B7-1 (CD80) and B7-2 (CD86). It is used for treatment of rheumatoid arthritis and juvenile rheumatoid arthritis.