The costimulatory role of TIM molecules

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Abstract
Summary: The T‐cell immunoglobulin domain and mucin domain (TIM) family, including TIM‐1, TIM‐2, TIM‐3, and TIM‐4, is a relatively newly described group of molecules with a conserved structure and important immunological functions, including T‐cell activation, induction of T‐cell apoptosis and T‐cell tolerance, and the clearance of apoptotic cells. TIM‐1 costimulates T‐cell activation and enhances cytokine production. In humans, TIM‐1 also serves as a susceptibility gene for allergy and asthma. TIM‐3, expressed on T cells and dendritic cells, regulates T‐cell apoptosis and immune tolerance. By contrast, TIM‐4, which is expressed primarily on antigen‐presenting cells and which is a receptor for phosphatidylserine, regulates T‐cell activation and tolerance, in part by mediating the uptake and engulfment of apoptotic cells. The TIM molecules thus have surprisingly broad activities affecting multiple aspects of immunology.