Intracellular signaling and endosomal trafficking of immunoreceptors: Shared effectors underlying MHC class II-restricted antigen presentation

Abstract

The cells of the immune system express a wide variety of receptors, defined as immunoreceptors because they are involved in antigen recognition. 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) molecules, through T-cell receptors (TcR). Many lymphoid or myeloid cells, such as B lymphocytes, macrophages or dendritic cells, express receptors for antigen–antibody complexes, which recognize the Fc portion of immunoglobulins (FcR). Although their ligands are different, immunoreceptors share both structural and functional homologies. The BcRs, TcRs and most FcRs, are multichain complexes composed of a ligand binding module, including one or two chains which determine the specificity of antigen recognition and a transducing module, which includes two to six chains containing a conserved motif in their cytoplasmic tail (A.D. Keegan and W.E. Paul, Immunol. Today 13 (1992) 63–68). This motif, called ITAM for immunoreceptor tyrosine-based activation motif (M.G. Reth, Nature 338 (1989) 383–384 and J.C. Cambier, Immunol. Today 16 (1995) 110–114) consists of five conserved amino acid residues precisely spaced over an amino acid sequence (D2xY2xL7x2xL). ITAMs couple receptors to intracellular effectors which induce a cascade of events leading to both cell activation and to down regulation of the receptors. This review focuses on recent data supporting the involvement of cytosolic effectors 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.