Tim-3

TIM-3 is the acronym for "T-cell immunoglobulin and mucin-domain containing-3". TIM-3 belongs to the family of anti-inflammatory immune checkpoints (ICs). Anti-inflammatory immune checkpoints inhibit the immune reactivity of T-lymphocytes, in contrast to pro-inflammatory ICs, which increase the immune reactivity of T-lymphocytes. The immune checkpoints are activated by precisely fitting cytokines (ligands) that are presented and released by other cells.

TIM-3, also known as "HAVCR2 = Hepatitis A virus cellular receptor 2", is a protein that in humans is encoded by the HAVCR2 gene. TIM-3 is a protein that belongs to a larger structurally related family(TIM family) of receptor poteins. TIM-3 is expressed on the cell surface of interferon-gamma producing CD4+ and CD8+ cells. Furthermore, Th17 cells, regulatory T cells and "innate" immune cells such as dendritic cells, NK cells and monocytes are also capable of expressing this protein.

The intracellular domain of HAVCR2 is referred to as the "C-terminal cytoplasmic tail". This protein portion contains 5 conserved tyrosine residues. It interacts with multiple components of the T cell receptor complex (TCR) and has a regulatory inhibitory effect on its function.

Mutations in the HAVCR2 gene are associated with the familial form of subcutaneous panniculitis-like T-cell lymphoma.

1. Gayden T et al (2019) Germline HAVCR2 mutations altering TIM-3 characterize subcutaneous panniculitis-like T cell lymphomas with hemophagocytic lymphohistiocytic syndrome. Nature Genet 50: 1650-1657.
2. Gautron AS et al (2014) Enhanced suppressor function of TIM-3+ FoxP3+ regulatory T cells. Eur J Immunol 44:2703-2711.
3. Gorman JV et al (2014) Regulation of T cell responses by the receptor molecule Tim-3. Immunol Res 59: 56-65.
4. Monney L et al (2002) Th1-specific cell surface protein Tim-3 regulates macrophage activation and severity of an autoimmune disease. Nature 415:536-541.
5. Polprasert C et al (2019) Frequent germline mutations of HAVCR2 in sporadic subcutaneous panniculitis-like T-cell lymphoma. Blood Adv 3: 588-595.
6. Sánchez-Fueyo A et al (2003) Tim-3 inhibits T helper type 1-mediated auto- and alloimmune responses and promotes immunological tolerance. Nat Immunol 4:1093-1101.