BIOLOGY OF THE INTERLEUKIN-2 RECEPTOR

摘要: Studies of the biology IL-2 receptor have played a major part in establishing several fundamental principles that govern our current understanding immunology. Chief among these is contribution made by lymphokines to regulation interactions vast numbers lymphocytes, comprising number functionally distinct lineages. These soluble mediators likely act locally, within context microanatomic organization primary and secondary lymphoid organs, where, combination with signals generated direct membrane-membrane interactions, wide spectrum cell fate decisions influenced. The properties as T-cell growth factor spawned view worked vivo promote clonal expansion during immune responses. Over time, this singular has suffered from increasing appreciation biologic effects IL-2R are much more complex than simply mediating growth: depending on set conditions, may also survival, effector function, apoptosis. sometimes contradictory underscore fact diversity intracellular signaling pathways potentially activated IL-2R. Furthermore, based integration multiple received lymphocyte environment; can thus be regarded one input process. In because was first identified factor, focus investigation IL-R2 been mechanism mitogenic cultured lines. Three critical events generation signal for cycle progression, including heterodimerization cytoplasmic domains beta gamma(c) chains, activation tyrosine kinase Jak3, phosphorylation residues chain. proximal led creation an complex, which various molecules recruited become substrates regulatory enzymes (especially kinases) associated receptor. One intriguing outcome studies performed lines apparent functional redundancy A H regions beta, their corresponding downstream pathways, respect proliferative response. Why should induce proliferation through or pathway? possibility unusual property lymphocytes require both optimal responses vivo. An alternative only redundant each region plays unique essential role regulating other aspects physiology. As examples, could prove important sensitivity AICD promoting development NK cells. issues resolved reconstituting beta-/-mice A-and H-deleted forms chain analyzing effect function addition nature regions, there remains large biochemical activities mediated no clear physiological identified. Therefore, circumstances ripe discovering new connections between molecular Translating Il-2R into how regulate system facilitated identification natural mutations components humans immunodeficiency mice targeted gen