INTRACELLULAR SIGNALING AND ENDOSOMAL TRAFFICKING OF IMMUNORECEPTORS SHARED EFFECTORS UNDERLYING MHC CLASS II-RESTRICTED ANTIGEN PRESENTATION

The cells of the immune system express a wide variety of receptors, de fined as immunoreceptors because they are involved in antigen recognit ion. B and T lymphocytes express clonally distributed receptors which recognize either soluble antigens, through B-cell receptors (BcR), or peptides associated to major histocompatibility complex (MHC) molecule s, through T-cell receptors (TcR). Many lymphoid or myeloid cells, suc h as B lymphocytes, macrophages or dendritic cells, express receptors for antigen-antibody complexes, which recognize the Fc portion of immu noglobulins (FcR). Although their ligands are different, immunorecepto rs share both structural and functional homologies. The BcRs, TcRs and most FcRs, are multichain complexes composed of a ligand binding modu le, including one or two chains which determine the specificity of ant igen recognition and a transducing module, which includes two to six c hains containing a conserved motif in their cytoplasmic tail (A.D. Kee gan and W.E. Paul, Immunol. Today 13 (1992) 63-68). This motif, called ITAM for immunoreceptor tyrosine-based activation motif (M.G. Reth, N ature 338 (1989) 383-384 and J.C. Cambier, Immunol. Today 16 (1995) 11 0-114) consists of five conserved amino acid residues precisely spaced over an amino acid sequence (D2xY2xL7x2xL). ITAMs couple receptors to intracellular effecters which induce a cascade of events leading to b oth cell activation and to down regulation of the receptors. This revi ew focuses on recent data supporting the involvement of cytosolic effe cters of cell activation in the endosomal transport of immunoreceptors . The possible role of these cytosolic factors in lysosomal transport and MHC class II restricted antigen presentation is discussed. (C) 199 7 Elsevier Science B.V.