T-lymphocyte activation antigen CD80 (CD80; B7-1) is type 1 transmembrane protein with an extracellular domain containing two Ig-like domains and shares ~25% sequence identity with its homolog CD86 (B7-2). (1) CD80 and CD86 are expressed on B‐cells, T‐cells, dendritic cells, and antigen presenting cells (APCs). (2) On APCs CD86 is constitutively expressed and upregulated in response to stimulation, while CD80 is later inducibly expressed. (2) (3) CD80, together with CD86 and B7-H2, serves as a ligand for CD28 and CTLA-4. (4) (5) Additionally CD80 can bind to PD-L1 with binding affinity being the strongest with CTLA-4, intermediate with PD-L1 and the lowest with CD28. (6) Binding of CD86, CD80 or B7-H2 to CD28 delivers a positive signal to T cells, in contrast, the interaction of CTLA-4 with B7 ligands attenuates T cell activation. (3) Also the interaction between CD80 and PD‐L1 provides an inhibitory signal, depicted by reduced T‐cell activation and cytokine production. (2) Interestingly CD80 and PD‐L1 can interact in the same cell as a mechanism to block interaction with PD‐1 or CTLA‐4 and corresponding T‐cell inhibition. (2) Blocking the CD80 interaction with CD28 is a target for the treatment of autoimmune diseases to facilitate organ transplantation and blocking the interactions with PD-L1 and CTLA-4 are targeted to restore antitumor responses (2).
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MGHTR – secretion signal sequence
TYCFA – intracellular domain
VIHVT – ectodomain
C — C – disulfide bond
LLPS – transmembrane domain
N – glycosylation site
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