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CTLA4 (Cytotoxic T-Lymphocyte Antigen 4) is a CD28-family receptor expressed on mainly CD4+ T cells. It binds the same ligands as CD28 (CD80 and CD86 on B cells and dendritic cells), but with higher affinity than CD28. However, in contrast to CD28 which enhances cell function when bound at the same time as the T cell receptor, CTLA4 inhibits the T cell and prevents it from functioning. Intracellular CTLA4 is also found in regulatory T cells and may be important to their function.
LAG-3 is a 70-kDa surface glycoprotein in the immunoglobulin superfamily, with structural homology to CD4. It binds to MHC class II molecules with higher affinity than CD4 and is involved in the negative regulation of T cell activation and homeostatic proliferation. LAG-3 is expressed on the surface of activated T cells, including regulatory T cells, and NK cells. Notably, CD8+ T cells express LAG-3 at significantly higher levels than CD4+ T cells. Additionally, the coexpression of LAG-3 and CD49b has been proposed as a marker for identifying Type 1 regulatory T cells (Tr1 cells) in both humans and mice. This highlights LAG-3s role in immune regulation and its potential as a target for therapeutic interventions in immune-related conditions.
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