Endocytosis of the class I major histocompatibility antigen via a phorbol myristate acetate-inducible pathway is a cell-specific phenomenon and requires the cytoplasmic domain [published erratum appears in J Cell Biol 1989 Sep;109(3):1381]

Abstract

Abstract. Class I major histocompatibility (MHC) antigens are expressed by virtually all mammalian cells, yet their levels of expression and behavior on the cell surface vary in a cell-specific fashion. A panel of lymphoid (both B and T) and nonlymphoid cell lines was used to study the kinetics of internalization of the H-2L d class I MHC in different cell types. These studies revealed that endocytosis of H-2L J occurs by both constitutive and PMA-regulated pathways in lymphoid cells, but only by a PMA-refractory pathway in the nonlymphoid cells tested. Transfectant derivatives of the T lymphoma, EL4, which express wild-type or mutant H-2L d class I MHC antigens, were used to investigate the requirement for the cytoplasmic domain of the class I MHC antigen for its endocytosis in T lymphocytes. These studies showed that modification or deletion of the cytoplasmic domain of H-2L ~ abrogates endocytosis via a PMA-regulated pathway. The role of cytoplasmic domain phosphorylation in PMAinducible endocytosis was examined. The wild-type H-2L d antigen is phosphorylated in all cell types examined, and this phosphorylation is up-regulated by PMA treatment. In contrast, cytoplasmic domain mutants of H-2L d fail to be phosphorylated in vivo, in the presence or absence of PMA. The universality of PMA-inducible hyperphosphorylation of the class I MHC antigen among diverse cell types leads us to conclude that phosphorylation of the cytoplasmic domain, while perhaps necessary, is not sufficient for triggering endocytosis via a PMA-inducible pathway. Furthermore, the results with the cytoplasmic domain mutants of H-2L ° suggest that a structural conformation of the class I MHC cytoplasmic domain is required for endocytosis via this route.

The PHD/LAP-Domain Protein M153R of Myxomavirus Is a Ubiquitin Ligase That Induces the Rapid Internalization and Lysosomal Destruction of CD4

“…Also, MHC-I molecules are known to be internalized, so the same model could apply to MHC-I. Since the rates of MHC-I internalization differ from cell type to cell type, it would be interesting to investigate how efficiently M153R downregulates MHC-I in different cell types (8). CD4 endocytosis is slowed down in the presence of the kinase Lck, which is present in T cells but not in HeLa cells (40).…”

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

“…Surface expression of MHC-I is also lost through internalization (20). Internalization of MHC-I occurs constitutively on activated lymphoid cells (23)(24)(25)(26)(27)). It appears that intact molecules are recycled to the cell surface and denatured molecules are shunted to a lysosomal pathway.…”

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.…”

“…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. More recently, studies have demonstrated that MHC-I down-modulation induced by the HIV protein Nef relies upon a conserved motif containing Tyr 320 located in the cytoplasmic tail (10,11).…”