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CD3 （cluster of differentiation 3） is a protein complex and T cell co-receptor that is involved in activating both the cytotoxic T cell （CD8+ naive T cells） and T helper cells （CD4+ naive T cells）. It is composed of four distinct chains. In mammals, the complex contains a CD3γ chain, a CD3δ chain, and two CD3ε chains. These chains associate with the T-cell receptor （TCR） and the CD3-zeta （ζ-chain） to generate an activation signal in T lymphocytes. The TCR, CD3-zeta, and the other CD3 molecules together constitute the TCR complex. The CD3–T cell receptor （TCR） complex plays a central role in the T-cell-mediated immunoresponse as it is involved in the recognition of antigens and subsequent signal transduction and activation of immunocompetent T lymphocytes. Because CD3 is required for T cell activation, drugs （often monoclonal antibodies） that target it are being investigated as immunosuppressant therapies （e.g., otelixizumab, teplizumab） for type 1 diabetes and other autoimmune diseases.