HLA class I deficiencies due to mutations in subunit 1 of the peptide transporter TAP1

Salle, Henri; Zimmer, Jacques; Fricker, Dominique; Angénieux, Catherine; Cazenave, Jean‐Pierre; Okubo, Mitsuo; Maeda, Hitoshi; Plebani, Alessandro; Tongio, M. M.; Dormoy, Anne; Hanau, Daniel

doi:10.1172/jci5687

Cited by 121 publications

(80 citation statements)

References 15 publications

(26 reference statements)

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“…4). We also compared the frequency of A2 multimer + CD4 and CD8 T cells in patients with decreased expression of surface MHC class I molecules, because of congenital deficiency for one subunit of the TAP peptide transporter (41). In line with previous studies, TAP deficiency led to a strongly decreased frequency of A2 multimer + CD8 T cells (42).…”

supporting

confidence: 60%

Impact of TCR Reactivity and HLA Phenotype on Naive CD8 T Cell Frequency in Humans

Legoux

Debeaupuis

Echasserieau

et al. 2010

The Journal of Immunology

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The impact of MHC phenotype on the shaping of the peripheral naive T cell repertoire in humans remains unknown. To address this, we compared the frequency and antigenic avidity of naive T cells specific for immunodominant self-, viral, and tumor Ags presented by a human MHC class I allele (HLA-A*02, referred to as A2) in individuals expressing or not this allele. Naive T cell frequencies varied from one Ag specificity to another but were restrained for a given specificity. Although A2-restricted T cells showed similar repertoire features and antigenic avidities in A2+ and A2− donors, A2 expression had either a positive, neutral, or negative impact on the frequency of A2-restricted naive CD8 T cells, depending on their fine specificity. We also identified in all donors CD4 T cells specific for A2/peptide complexes, whose frequencies were not affected by MHC class I expression, but nevertheless correlated with those of their naive CD8 T cell counterparts. Therefore, both selection by self-MHC and inherent TCR reactivity regulate the frequency of human naive T cell precursors. Moreover this study also suggests that T cell repertoire shaping by a given self-MHC allele is dispensable for generation of immunodominant T cell responses restricted by this particular allele.

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supporting

confidence: 60%

Impact of TCR Reactivity and HLA Phenotype on Naive CD8 T Cell Frequency in Humans

Legoux

Debeaupuis

Echasserieau

et al. 2010

The Journal of Immunology

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“…Schultz et al (2003) found that patients without TAP are more likely to become infected by gram-negative bacteria because bactericidal/permeability-increasing protein activity was inhibited. In addition, patients without TAP are more likely to be infected by gram-negative bacteria than by a virus (de la Salle et al, 1994Salle et al, , 1999. E. coli F18 mainly infects the duodenum and jejunum.…”

Section: Discussionmentioning

confidence: 99%

Dynamic changes in TAP1 expression levels in newborn to weaning piglets, and its association with Escherichia coli F18 resistance

Wang¹,

Liu²,

Dong³

et al. 2014

Genet. Mol. Res.

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ABSTRACT. The transporter associated with antigen processing (TAP) transports peptides from the cytosol into the endoplasmic reticulum for subsequent loading onto the major histocompatibility complex (MHC) class I molecules. This study showed the dynamic changes in the TAP1 expression level in newborn to weaning piglets. Tissue expression profiles revealed that the TAP1 gene was expressed at low levels in all tissues, and the expression levels were relatively higher in the lung, spleen, lymph, and thymus; further, no significant difference was observed in the expression in each tissue among the 3 unweaned stages (8, 18, and 30 days). Nevertheless, the postweaning (35 days) expression levels in tissues, including the spleen, lung, lymph, duodenum, and jejunum were significantly higher than those in the unweaned stages. Furthermore, gene ontology and pathway analysis showed that TAP1 took part in 38 biological functions and 5 pathway processes, including ABC transporters and antigen processing and presentation. These analyses showed that the TAP1 gene, which was 3687 ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 13 (2): 3686-3692 (2014) TAP1 gene related to Escherichia coli F18 resistance related to MHC I immune regulation, had a stable and low expression level in unweaned stages; however, its expression increased in the postweaning stages. The high expression level of TAP1 indicated that the gene might play an important role in Escherichia coli F18 resistance.

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“…HLA class I biosynthesis is disrupted in multiple TAP1-deficient cell lines (10,35,36). To determine whether the tobaccomediated reduction in TAP1 caused similar changes in HLA class I biosynthesis, we compared assembly, maturation, and stability in tobacco-treated and untreated cells (Fig.…”

Section: Discussionmentioning

confidence: 99%

Tobacco Reduces Membrane HLA Class I That Is Restored by Transfection with Transporter Associated with Antigen Processing 1 cDNA

Fine

Han

Sun

et al. 2002

The Journal of Immunology

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HLA class I molecules are recognized by CTL that eliminate virally infected and malignantly transformed cells presenting foreign peptide—a process termed immunosurveillance. Many tumors have reduced levels of membrane HLA class I. Tumor cells with mutations that reduce HLA class I avoid immunosurveillance and continue to proliferate. As tobacco use can induce tumors, we examined the effect of tobacco extracts on membrane HLA class I. These studies show that culture of cells in media containing tobacco extracts reduces membrane HLA class I, but not other proteins, on primary keratinocytes and other cell types. Culture in tobacco extracts, but not extracts of other substances, reduces TAP1 protein, but does not reduce expression of HLA class I H chain, L chain, or the housekeeping protein β-actin. The reduction of TAP1 protein occurs within 4 h and is dose-dependent. Culture in tobacco extracts reduces TAP1 protein abundance, but not steady-state mRNA abundance. Tobacco-treated cells show defects in HLA class I biosynthesis similar to those found in TAP1-deficient cell lines. Transfection with TAP1 cDNA restores TAP1 protein abundance, HLA class I biosynthesis, and cell surface expression. Combined, these data show that culture in tobacco extracts reduces TAP1 protein abundance and membrane HLA class I levels. Reduction in membrane HLA class I could permit subsequent malignant transformation of cells to be undetected by the immune system.

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HLA class I deficiencies due to mutations in subunit 1 of the peptide transporter TAP1

Cited by 121 publications

References 15 publications

Impact of TCR Reactivity and HLA Phenotype on Naive CD8 T Cell Frequency in Humans

Impact of TCR Reactivity and HLA Phenotype on Naive CD8 T Cell Frequency in Humans

Dynamic changes in TAP1 expression levels in newborn to weaning piglets, and its association with Escherichia coli F18 resistance

Tobacco Reduces Membrane HLA Class I That Is Restored by Transfection with Transporter Associated with Antigen Processing 1 cDNA

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