Major histocompatibility complex class I molecules internalized via coated pits in T lymphocytes

Abstract

Endocytosis of the major histocompatibility complex (MHC)-encoded class I and class II molecules has been the subject of recent investigations. Class I molecules, which are key elements in T cell-mediated cytotoxicity, are differentially endocytosed by different cell types. Fibroblasts internalize their class I molecules via uncoated cell surface vesicles and tubular invaginations when these molecules are cross-linked with multivalent ligands. T lymphocytes internalize their class I molecules spontaneously, but B lymphocytes do not internalize them at all. Here we describe a morphological investigation of the mechanism by which class I molecules are endocytosed by T lymphocytes. We show that, unlike fibroblasts, T lymphocytes spontaneously internalize 20-40% of their class I molecules in a process involving coated pits and coated vesicles. Thus, the endocytic pathway of class I molecules in T lymphocytes is similar to those of other more classical cell-surface receptors involved in receptor-mediated endocytosis. In contrast, the same class I molecules remained on the cell surface in B lymphocytes. These data show that class I molecules are differentially regulated in T and B lymphocytes and fibroblasts.

Mobilization of MHC class I molecules from late endosomes to the cell surface following activation of CD34-derived human Langerhans cells

“…It was therefore of considerable interest to identify an endosomal pool of class I molecules in CD34-derived LCs that was not apparent in monocyte-derived DCs. Endocytosis and recycling of class I molecules has been seen on many cell types, including B lymphoblastoid cells (32), monocytes, and macrophages where class I is internalized via coated pits, and up to 30% of class I may be recycled (33). More recently, a role for phosphorylation as a signal for recycling class I molecules has been suggested (34).…”

Stability of Surface H-2Kb, H-2Db, and Peptide-Receptive H-2Kb on Splenocytes

“…Denatured material is then routed to lysosomes. Endocytosis is via clathrincoated pits (45) and depends upon a motif present in the cytoplasmic tail of the MHC-I molecule (46). Other cells can also recycle MHC-I.…”

Lack of Tyrosine 320 Impairs Spontaneous Endocytosis and Enhances Release of HLA-B27 Molecules

“…Endocytosis of MHC-I molecules has long been recognized, and occurs in a variety of different cell types (5)(6)(7)(8)(9). The process has biological implications for endosomal and lysosomal peptide loading and display, with the latter event designated as cross-presentation (14,33).…”

“…The rate of spontaneous endocytosis of MHC-I molecules is higher in lymphoid T cells and monocytes than in B cells and can be induced by activation of protein kinase C-regulated pathways (5)(6)(7)(8)(9). Zuniga and colleagues (5) were the first to report that endocytosis of MHC-I molecules required the cytoplasmic domain and suggested that a conformational change was required for endocytosis.…”