Factors Controlling the Trafficking and Processing of a Leader-Derived Peptide Presented by Qa-1

Bai, Ailin; Aldrich, Carla J.; Forman, James

doi:10.4049/jimmunol.165.12.7025

Cited by 11 publications

(7 citation statements)

References 72 publications

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“…Because extension at the C terminus dramatically reduces the peptide-binding affinity to HLA-E, it is likely that C-terminal trimming occurs in the cytosol. This would be consistent with previous reports suggesting that the generation of the Qdm peptide binding to Qa-1 involves cytosolic C-terminal trimming (41) and that ER-resident proteases can trim peptides at their N terminus and not at the C terminus (31-33, 36, 42). Conversely, N-terminal trimming could occur in the cytosol or the ER and may even take place after binding of the peptide to HLA-E since N-terminal extensions do not appear to affect peptide binding (30 -33, 36, 43).…”

Section: Discussionsupporting

confidence: 81%

“…One aspect that still needs to be investigated is whether SPPase can generate both TAP-dependent and TAP-independent signal peptide fragments capable of binding to MHC class I molecules. Interestingly, removing the charged residue (Arg at position 7) in the N-terminal region of the mouse HLA class I signal sequence alters its insertion and induces TAP-independent presentation of the Qdm peptide (41,44). The human cytomegalovirus glycoprotein UL40 (HCMV gpUL40) also provides such signal peptide in a TAP-independent manner (45,46).…”

Section: Discussionmentioning

confidence: 99%

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Intramembrane Proteolysis of Signal Peptides: An Essential Step in the Generation of HLA-E Epitopes

Lemberg

Bland

Weihofen

et al. 2001

The Journal of Immunology

173

150

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Signal sequences of human MHC class I molecules are a unique source of epitopes for newly synthesized nonclassical HLA-E molecules. Binding of such conserved peptides to HLA-E induces its cell surface expression and protects cells from NK cell attack. After cleavage from the pre-protein, we show that the liberated MHC class I signal peptide is further processed by signal peptide peptidase in the hydrophobic, membrane-spanning region. This cut is essential for the release of the HLA-E epitope-containing fragment from the lipid bilayer and its subsequent transport into the lumen of the endoplasmic reticulum via the TAP.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Intramembrane Proteolysis of Signal Peptides: An Essential Step in the Generation of HLA-E Epitopes

Lemberg

Bland

Weihofen

et al. 2001

The Journal of Immunology

173

150

View full text Add to dashboard Cite

show abstract

“…These are structurally similar to class I molecules but bind hydrophobic peptides, N-formylated peptides, or signal peptides of class Ia molecules, respectively. When their cognate peptides are not available, they are retained in the ER (53)(54)(55)(56)(57)(58). Similarly, the stability of class II molecules is determined by peptide exchange mediated in the endocytic pathway by DM molecules.…”

Section: Discussionmentioning

confidence: 99%

Calnexin, Calreticulin, and ERp57 Cooperate in Disulfide Bond Formation in Human CD1d Heavy Chain

Kang

Cresswell

2002

Journal of Biological Chemistry

116

110

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Members of the CD1 family of membrane glycoproteins can present antigenic lipids to T lymphocytes. Like major histocompatibility complex class I molecules, they form a heterodimeric complex of a heavy chain and ␤ 2 -microglobulin (␤ 2 m) in the endoplasmic reticulum (ER). Binding of lipid antigens, however, takes place in endosomal compartments, similar to class II molecules, and on the plasma membrane. Unlike major histocompatibility complex class I or CD1b molecules, which need ␤ 2 m to exit the ER, CD1d can be expressed on the cell surface as either a free heavy chain or associated with ␤ 2 m. These differences led us to investigate early events of CD1d biosynthesis and maturation and the role of ER chaperones in its assembly. Here we show that CD1d associates in the ER with both calnexin and calreticulin and with the thiol oxidoreductase ERp57 in a manner dependent on glucose trimming of its N-linked glycans. Complete disulfide bond formation in the CD1d heavy chain was substantially impaired if the chaperone interactions were blocked by the glucosidase inhibitors castanospermine or N-butyldeoxynojirimycin. The formation of at least one of the disulfide bonds in the CD1d heavy chain is coupled to its glucose trimmingdependent association with ERp57, calnexin, and calreticulin.

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“…Numerous antigenic peptides derived from signal sequences and presented in a TAP-independent manner have since been reported [48,[109][110][111][112]. Conversely, presentation of several peptide antigens derived from signal sequences is dependent on TAP function [113][114][115] and carboxyl terminal trimming in the cytosol [116], indicating the existence of a still poorly characterized mechanism for retrograde transport of peptides from the ER to the cytosol. ER proteolytic activity is primarily that of aminopeptidase while carboxypeptidase activity is limited [117].…”

Section: Processing and Presentation Of Membrane Proteins In The Er Amentioning

confidence: 99%

The contributions of mass spectrometry to understanding of immune recognition by T lymphocytes

Engelhard

2007

International Journal of Mass Spectrometry

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Over the last 15 years, the ability of mass spectrometry to analyze complex peptide mixtures and identify individual species has provided unprecedented insights into the repertoire of peptide antigens displayed by MHC molecules and recognized by T lymphocytes. These include: understanding the peptide binding specificity of MHC molecules; understanding of roles of different intracellular components of the antigen processing pathways in determining the peptide display; and identification of a large number of individual peptide antigens associated with infectious diseases, cancer, and transplant rejection that have provided the basis for new immunologically based therapies. This review will summarize the impact that the application of mass spectrometry has had on these advances, with particular attention to the contributions of Professor Donald Hunt and members of his laboratory, and point out the opportunities for future work. Keywordsantigen processing; post-translational modification; peptides; MHC molecules THE NATURE OF ANTIGEN RECOGNITION BY T LYMPHOCYTEST lymphocytes are a branch of the immune system concerned with recognition of antigens that are displayed on the surface of host cells. These antigens are produced through intracellular proteolytic mechanisms that create small peptides, which are then rescued and presented at the cell surface by adaptor proteins called MHC molecules [reviewed in [1-6]. The binding site of each MHC molecule enables it to bind to a wide range of different peptides, and results in the display of a repertoire of such antigens, each recognized by a distinct T lymphocyte. This "antigen processing and presentation" mechanism results in the display of peptides derived from the proteins of pathogens that have infected the cell or been taken up by endocytosis. Their recognition by T lymphocytes results in the development of an immune response, and results in clearance of the pathogen and infected cells from the body. However, antigen processing and presentation pathways operate constitutively on normal cellular proteins as well, resulting in the display of peptide antigens that can be distinguished on tumors and transplanted tissues. Some of these "self-peptides" are also involved in the development of T lymphocytes in the thymus, and their recognition also controls the balance between selftolerance and autoimmune disease. Correspondence: phone: 434-924-2423; fax: 434-924-1221; email: vhe@virginia.edu Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. In most individuals, molecules of each MHC class are expressed from 3 genetic loci that ...

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Factors Controlling the Trafficking and Processing of a Leader-Derived Peptide Presented by Qa-1

Cited by 11 publications

References 72 publications

Intramembrane Proteolysis of Signal Peptides: An Essential Step in the Generation of HLA-E Epitopes

Intramembrane Proteolysis of Signal Peptides: An Essential Step in the Generation of HLA-E Epitopes

Calnexin, Calreticulin, and ERp57 Cooperate in Disulfide Bond Formation in Human CD1d Heavy Chain

The contributions of mass spectrometry to understanding of immune recognition by T lymphocytes

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