After a lymphocyte recognizes antigen on the surface of a somatic cell or on an """"""""antigen presenting cell"""""""", an efficient immune response depends on attraction of other immunological cells to the site of recognition. Immunectin secretion is a likely candidate for such an attractant. It is rapidly and abundantly transcribed and secreted after activation of T-lymphocytes and Thy+ NK cell clones but not B cells, mast cell clones or fibroblasts. The recombinant molecule is released into the supernatant after expression of the cDNA is COS cells and this is consistent with the molecule having the structural features of a secreted protein. Immunectin is extremely hydrophilic and has a single N-linked glycosylation site. Immunectin contains the tripeptide sequence ARg-Gly-Asp (RGD), which marks a family of extracellular adhesives and causes specific cell types to migrate and express new genes. In all case studies, the RGD tripeptide is a critical part of the molecule's binding site to target cell. Immunectin is no exception. Mast cells and macrophages carry about 105 immunectin receptors which bind to the ligand with a Kd of 10-12. Binding results in migration of cells across an immunectin gradient towards the source of immunectin production. The hydrophilic nature of recombinant immunectin makes it unlikely that a gradient formed around an activated T- cell in vivo would be disturbed by non-specific interaction with hydrophobic molecules or cells. Moreover, studies of monocytes that migrate in an immunectin gradient show that binding to immunectin at appropriate concentrations activates them to become phagocytic and express surface IA molecules. Taken together, this evidence indicates that immunectin production by T-cells after activation by foreign antigen to be responsible for recruitment of immunologic effector cells including mast cells and macrophages to the site of activation. In summary, the immune response triggered by recirculating lymphocytes is marked by the secretion of large amounts of immunectin which binds with high affinity to immunologic effector cells. We will define the role of immunectin in inflammatory and allergic immune responses in vitro and in animals, and further characterize the structural basis of immunectin activity.
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