Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4; CD152) is a type I transmembrane protein which belongs to the immunoglobulin (Ig) superfamily and bears a single Ig-V (variable)-like extracellular domain. (1) (2) CTLA-4 is CD28 homolog and shares both its ligands, CD80 and CD86, with CD28. CTLA-4 forms a homodimer on activated T cells and binds to two ligands having higher affinity and avidity for the ligands than CD28. (2) Engagement of ligands by CTLA-4 results in T cell inhibition as opposite to the CD28/Ligand formation which activates T cells. (3) Amount of CD28/Ligand binding versus CTLA-4/Ligand binding determines whether a T cell will undergo activation or anergy. (4) Additionally the third ligand for CTLA-4 (and CD28) was discovered, B7-H2 (ICOS-Ligand), which primarily binds to ICOS. (5) ICOS binds to B7-H2 with significantly higher affinity than does CD28 or CTLA-4. (5) Molecules that block CTLA-4 are needed for treatment of various types of cancer including melanoma, lung cancer kidney cancer, prostate cancer, and head and neck cancer (4).
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MACLG – secretion signal sequence
VSLSKM – intracellular domain
KAMHV – ectodomain
C — C – disulfide bond
FLLWI – transmembrane domain
N – glycosylation site