Differential endocytosis of T and B lymphocyte surface molecules evaluated with antibody-bearing fluorescent liposomes containing methotrexate.

Machy, Patrick; Barbet, Jacques; Leserman, Lee

doi:10.1073/pnas.79.13.4148

Cited by 69 publications

(25 citation statements)

References 28 publications

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“…Endocytosis of MHC class I molecules has been studied using several cell types as models, including lymphocytes, fibroblasts, and macrophages, with variability reported for the extent and pathway of internalization (35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46). The endocytosis of MHC class I molecules is dependent on a sequence in the MHC class I molecule cytoplasmic tail (40,41,47).…”

Section: Discussionmentioning

confidence: 99%

Mechanism for Amyloid Precursor-like Protein 2 Enhancement of Major Histocompatibility Complex Class I Molecule Degradation

Tuli

Sharma

Capek

et al. 2009

Journal of Biological Chemistry

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Earlier studies have demonstrated interaction of the murine major histocompatibility complex (MHC) class I molecule K d with amyloid precursor-like protein 2 (APLP2), a ubiquitously expressed member of the amyloid precursor protein family. Our current findings indicate that APLP2 is internalized in a clathrindependent manner, as shown by utilization of inhibitors of the clathrin pathway. Furthermore, we demonstrated that APLP2 and K d bind at the cell surface and are internalized together. The APLP2 cytoplasmic tail contains two overlapping consensus motifs for binding to the adaptor protein-2 complex, and mutation of a tyrosine shared by both motifs severely impaired APLP2 internalization and ability to promote K d endocytosis. Upon increased expression of wild type APLP2, K d molecules were predominantly directed to the lysosomes rather than recycled to the plasma membrane. These findings suggest a model in which APLP2 binds K d at the plasma membrane, facilitates uptake of K d in a clathrin-dependent manner, and routes the endocytosed K d to the lysosomal degradation pathway. Thus, APLP2 has a multistep trafficking function that influences the expression of major histocompatibility complex class I molecules at the plasma membrane.The efficacy of the cellular immune response to intracellular pathogens and tumors is reliant on major histocompatibility complex (MHC) 5 class I molecules. MHC class I molecules present peptides, including peptides derived from pathogens and tumors, at the cell surface to cytotoxic T lymphocytes.Cytotoxic T lymphocytes have been selected during development for their ability to react to cells in the periphery expressing self MHC class I molecules bearing non-self peptides. The level of cell surface expression of MHC class I molecules on infected and malignant cells therefore dictates the extent to which the antigen-specific cytotoxic T lymphocytes can recognize, and subsequently lyse, abnormal cells. The cell surface expression of MHC class I molecules is controlled by the quantity and quality of MHC class I molecules that are assembled, and also by the rate at which MHC class I molecules depart from the plasma membrane.Amyloid precursor-like protein 2 (APLP2) binds to the MHC class I molecule K d in cells that express ␤2-microglobulin (1, 2). APLP2 regulates the level of folded K d molecules at the cell surface: a reduction in APLP2 expression causes an elevation in the amount of folded K d at the plasma membrane, and an increase in APLP2 expression results in a decline in folded K d surface expression (3, 4). Higher APLP2 expression lowers the level of K d at the plasma membrane by increasing the endocytosis, destabilization, and turnover of K d molecules (4). The family of proteins to which APLP2 belongs includes APL-1 in Caenorhabditis elegans, APPL in Drosophila, and three proteins in mammals: amyloid precursor protein (APP), amyloid precursor-like protein 1, and APLP2 (5, 6). APLP2 shares a high degree of sequence homology with APP, particularly at the C-terminal end. However, ...

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Section: Discussionmentioning

confidence: 99%

Mechanism for Amyloid Precursor-like Protein 2 Enhancement of Major Histocompatibility Complex Class I Molecule Degradation

Tuli

Sharma

Capek

et al. 2009

Journal of Biological Chemistry

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“…T cell surface MHC class I molecules are subjected to spontaneous cycles of endocytosis/re-expression via coated pits (39,(51)(52)(53). Moreover, endocytosed ␤ 2 m-associated MHC class I molecules are re-expressed at the cell surface as ␤ 2 m-free unfolded MHC class I molecules (54, 55).…”

Section: Calreticulin Expression In Human Peripheral Blood T Lymphocymentioning

confidence: 99%

Calreticulin Is Expressed on the Cell Surface of Activated Human Peripheral Blood T Lymphocytes in Association with Major Histocompatibility Complex Class I Molecules

Arosa

Jesús

Porto

et al. 1999

Journal of Biological Chemistry

130

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Calreticulin is an endoplasmic reticulum resident molecule known to be involved in the folding and assembly of major histocompatibility complex (MHC) class I molecules. In the present study, expression of calreticulin was analyzed in human peripheral blood T lymphocytes. Pulse-chase experiments in [35 S]methionine-labeled T cell blasts showed that calreticulin was associated with several proteins in the endoplasmic reticulum and suggested that it was expressed at the cell surface. Indeed, the 60-kDa calreticulin was labeled by cell surface biotinylation and precipitated from the surface of activated T cells together with a protein with an apparent molecular mass of 46 kDa. Cell surface expression of calreticulin by activated T lymphocytes was further confirmed by immunofluorescence and flow cytometry, studies that showed that both CD8؉ and CD4؉ T cells expressed calreticulin in the plasma membrane. Low amounts of cell surface calreticulin were detected in resting T lymphocytes. By sequential immunoprecipitation using the conformation independent monoclonal antibody HC-10, we provided evidence that the cell surface 46-kDa protein co-precipitated with calreticulin is unfolded MHC I. These results show for the first time that after T cell activation, significant amounts of calreticulin are expressed on the T cell surface, where they are found in physical association with a pool of ␤ 2 -free MHC class I molecules.Calreticulin is a highly conserved and widely tissue distributed calcium-binding protein with a C-terminal KDEL endoplasmic reticulum (ER) 1 retrieval sequence (1-3). However, calreticulin has also been found outside the ER, such as within the secretory granules of cytotoxic lymphocytes, the cell surface of melanoma cells and virus-infected fibroblasts, and the cytosol and nucleus of several cell types reviewed in Ref. 9). Given its lectin-like properties, calreticulin is considered to be an ER chaperone involved in the assembly and folding of nascent glycoproteins (10 -13).Mature MHC class I molecules are composites of a 44 -49-kDa polymorphic heavy chain and a 12-kDa light chain (␤ 2 m) complexed with a cytosolic-processed peptide that are expressed on the plasma membrane of almost every nucleated cell (14). A number of ER resident molecular chaperones, such as calnexin, BiP, and transporter-associated protein, are involved in the assembly of the different composites (15)(16)(17)(18). Recently, calreticulin has also been shown to function as a chaperone in the assembly and folding of MHC class I molecules in the ER (19 -22). Contrary to calnexin, calreticulin binds to MHC class I-␤ 2 m dimers and to transporter-associated protein via another chaperone, tapasin (19,21). After peptide loading and deglucosylation of N-linked glycans, calreticulin dissociates from the MHC class I-␤ 2 m dimers, thus allowing the final transport of mature MHC class I molecules to the cell surface (20).Recent studies on the biosynthesis of TcR⅐CD3 complexes suggest that some chaperones such as calnexin can escape the ER retent...

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“…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).…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

mentioning

confidence: 99%

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

Santos

Antoniou

Sampaio³

et al. 2006

The Journal of Immunology

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Several lines of evidence suggest that endocytosis of MHC class I molecules requires conserved motifs within the cytoplasmic domain. In this study, we show, in the C58 rat thymoma cell line transfected with HLA-B27 molecules, that replacement of the highly conserved tyrosine (Tyr320) in the cytoplasmic domain of HLA-B27 does not hamper cell surface expression of β2-microglobulin H chain heterodimers or formation of misfolded molecules. However, Tyr320 replacement markedly impairs spontaneous endocytosis of HLA-B27. Although wild-type molecules are mostly internalized via endosomal compartments, Tyr320-mutated molecules remain at the plasma membrane in which partial colocalization with endogenous transferrin receptors can be observed, also impairing their endocytosis. Finally, we show that Tyr320 substitution enhances release of cleaved forms of HLA-B27 from the cell surface. These studies show for the first time that Tyr320 is most likely part of a cytoplasmic sorting motif involved in spontaneous endocytosis and shedding of MHC class I molecules.

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Differential endocytosis of T and B lymphocyte surface molecules evaluated with antibody-bearing fluorescent liposomes containing methotrexate.

Cited by 69 publications

References 28 publications

Mechanism for Amyloid Precursor-like Protein 2 Enhancement of Major Histocompatibility Complex Class I Molecule Degradation

Mechanism for Amyloid Precursor-like Protein 2 Enhancement of Major Histocompatibility Complex Class I Molecule Degradation

Calreticulin Is Expressed on the Cell Surface of Activated Human Peripheral Blood T Lymphocytes in Association with Major Histocompatibility Complex Class I Molecules

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

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