HLA class I deficiencies due to mutations in subunit 1 of the peptide transporter TAP1. J Clin Invest 103:R9-R13

Laboratoire des Cellules Dendritiques, INSERM CJF 94-03.
Journal of Clinical Investigation (Impact Factor: 13.22). 04/1999; 103(5):R9-R13. DOI: 10.1172/JCI5687
Source: PubMed

ABSTRACT The transporter associated with antigen processing (TAP), which is composed of two subunits (TAP1 and TAP2) that have different biochemical and functional properties, plays a key role in peptide loading and the cell surface expression of HLA class I molecules. Three cases of HLA class I deficiency have previously been shown to result from the absence of a functional TAP2 subunit. In the present study, we analyzed two cases displaying not only the typical lung syndrome of HLA class I deficiency but also skin lesions, and found these patients to be TAP1-deficient. This defect leads to unstable HLA class I molecules and their retention in the endoplasmic reticulum. However, the absence of TAP1 is compatible with life and does not seem to result in higher susceptibility to viral infections than TAP2 deficiency. This work also reveals that vasculitis is often observed in HLA class I-deficient patients.

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    • "Con Hm Exon 2: Cytosine at 819 Nt Exon 1/Exon 2: G at 778 Nt TAP1 not detected [45] [46] "
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    Immunology letters 01/2012; 141(2):147-57. DOI:10.1016/j.imlet.2011.10.007 · 2.51 Impact Factor
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    • "However, expression of single TAP2 is not possible in this cell line. Furthermore, expression of TAP2 is not observed in cells isolated from Bare Lymphocytes Syndrome (BLS) type I patients lacking the expression of TAP1 [41] [42]. In the human melanoma cell line buf1280, the TAP1 gene has a deletion mutation at position 1489, leading to a frame shift and to an early stop codon [43]. "
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    ABSTRACT: The transporter associated with antigen processing (TAP) is a key factor of the major histocompatibility complex (MHC) class I antigen presentation pathway. This ABC transporter translocates peptides derived mainly from proteasomal degradation from the cytosol into the ER lumen for loading onto MHC class I molecules. Manifold mechanisms have evolved to regulate TAP activity. During infection, TAP expression is upregulated by interferon-gamma. Furthermore, the assembly and stability of the transport complex is promoted by various auxiliary factors. However, tumors and viruses have developed sophisticated strategies to escape the immune surveillance by suppressing TAP function. The activity of TAP can be impaired on the transcriptional or translational level, by enhanced degradation or by inhibition of peptide translocation. In this review, we briefly summarize existing data concerning the regulation of the TAP complex.
    FEBS Letters 03/2006; 580(4):1156-63. DOI:10.1016/j.febslet.2005.11.048 · 3.17 Impact Factor
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