Splice acceptor site mutation of the transporter associated with antigen processing-1 gene in human bare lymphocyte syndrome

Furukawa, Hiroshi; Murata, Shigeo; Yabe, Toshikazu; Shimbara, Naoki; Keicho, Naoto; Kashiwase, Kouichi; Watanabe, Kaoru; Ishikawa, Yoshihide; Akaza, Tatsuya; Tadokoro, Kenji; Tohma, Shigeto; Inoue, Tomoshige; Tokunaga, Katsushi; Yamamoto, Kazuhiko; Tanaka, Keiji; Juji, Takeo

doi:10.1172/jci5335

Cited by 54 publications

(36 citation statements)

References 21 publications

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“…3B). Although TAP2 is expressed in the SK19 cells, very low levels of either HLA-B*4402 or HLA-B*4405 were recovered in the anti-TAP2 immunoprecipitates (data not shown), consistent with the likely requirement for TAP1 for stable expression of TAP2 (34). Tapasin binding was quantified by metabolic labeling of cells, PaSta-1 immunoprecipitations, and secondary immunoprecipitations with anti-HA (Fig.…”

Section: Both Hla-b*4402 and Hla-b*4405 Form Bonafide Peptideloading supporting

confidence: 58%

HLA-B44 Polymorphisms at Position 116 of the Heavy Chain Influence TAP Complex Binding via an Effect on Peptide Occupancy

Thammavongsa

Raghuraman

Filzen

et al. 2006

The Journal of Immunology

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A single residue polymorphism distinguishes HLA-B*4402(D116) from HLA-B*4405(Y116), which was suggested to allow HLA-B*4405 to acquire peptides without binding to tapasin-TAP complexes. We show that HLA-B*4405 is not inherently unable to associate with tapasin-TAP complexes. Under conditions of peptide deficiency, both allotypes bound efficiently to TAP and tapasin, and furthermore, random nonamer peptides conferred higher thermostability to HLA-B*4405 than to HLA-B*4402. Correspondingly, under conditions of peptide sufficiency, more rapid peptide-loading, dissociation from TAP complexes, and endoplasmic reticulum exit were observed for HLA-B*4405, whereas HLA-B*4402 showed greater endoplasmic reticulum retention and enhanced tapasin-TAP binding. Together, these studies suggest that position 116 HLA polymorphisms influence peptide occupancy, which in turn determines binding to tapasin and TAP. Relative to HLA-B*4405, inefficient peptide loading of HLA-B*4402 is likely to underlie its stronger tapasin dependence for cell surface expression and thermostability, and its enhanced susceptibility to pathogen interference strategies.

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Section: Both Hla-b*4402 and Hla-b*4405 Form Bonafide Peptideloading supporting

confidence: 58%

HLA-B44 Polymorphisms at Position 116 of the Heavy Chain Influence TAP Complex Binding via an Effect on Peptide Occupancy

Thammavongsa

Raghuraman

Filzen

et al. 2006

The Journal of Immunology

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“…2A, B), possibly due to the unstable conformation of the TAP2 moiety without TAP1 in vivo 19,36) and in vitro, 20) while the TAP1 molecule in TAP2-deficient cells was stable. 19,37) Furthermore, TM6-9 of TAP2 was also localized in the cytosol, although TM1 of TAP2 was retained on the ER.…”

Section: Membrane Localization Of Tapl and Its Truncated Formsmentioning

confidence: 99%

Membrane Localization of Transporter Associated with Antigen Processing (TAP)-Like (ABCB9) Visualized in Vivo with a Fluorescence Protein-Fusion Technique

Kobayashi

Maeda

2004

Biological & Pharmaceutical Bulletin

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The ATP binding cassette (ABC) transporter superfamily comprises a large family of transmembrane proteins that transport a variety of substrates across membranes coupled with ATP hydrolysis. 1,2) This superfamily is related to the drug resistance of cancer cells and pathogens, immune responses and some congenital disorders. [3][4][5] Human ABC transporters have been classified into seven subfamilies (A-G) based on the sequences and organizations of their ATP binding domains.6,7) Subfamily B consists of half-and fulltype transporters, well-characterized members being transporter associated with antigen processing (TAP) 8) and multidrug resistance (MDR), 9) respectively. The members of this subfamily transport a variety of cationic substrates of different sizes, from iron to antibiotics, anti-tumor compounds and antigenic polypeptides.TAPL (TAP-like; ABCB9) is strongly homologous to TAP1 and TAP2; 60 and 62%, respectively, of their amino acid residues are conserved.10) From such similarity, it is expected that a potential function of TAPL could be associated with peptide transport like in the case of TAP. Furthermore, it is noteworthy that TAPL is highly conserved in rodents and man (95% identity in amino acid residues), compared with TAP1 and TAP2 (75% and 77% identity, respectively), suggesting that the evolutional rate of TAPL was much slower than those of TAP1 and TAP2, although TAPL could have diverged from an ancestor of TAP.11) Recently we found the novel splicing isoforms with different carboxyl-terminal sequences in rat and human, 12,13) although the major isoform was originally reported one.Most of the half-type ABC transporters are localized to intracellular organelle membranes and function as either homodimers or heterodimers. [14][15][16] In this study we examined the cellular distributions of TAPL and its family members (TAP1 and TAP2), and their mutual interactions by monitoring the fluorescence derived from fluorescent proteins fused downstream of the carboxyl terminal cytoplasmic ABC region or of the amino terminal transmembrane region. Although TAP1 and TAP2 form a heterodimer, [17][18][19][20] and TAPL, TAP1 and TAP2 show strong sequence similarity to each other, 11) it has not been determined whether TAPL forms a heterodimer or a homodimer. MATERIALS AND METHODSCell Culture, Transfection and Preparation of Total RNA Cells were grown in Dulbecco's modified Eagle's medium (GIBCO BRL) containing 7% (v/v) fetal bovine serum (JRH Bioscience). COS-1 cells (ATCC) 21) were transfected by the DEAE-dextran method as described previously.22) HEK-293 cells (2-5ϫ10 5 cells/F 60 mm dish) (RIKEN Cell Bank) 23) were transfected by the cationic lipid method using 2.5 mg/dish plasmid DNA with UltraFector or SuperFector (B-bridge), as recommended by the manufacturer. Cells were further grown for 24 h, and then subjected to Western blotting or microscopic observation.Total RNA was extracted with Isogen (Wako Chemicals) 24) from HEK-293 cells cultured in two F10 cm dishes. First strand cDNA was synthesized from 5 m...

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“…Respectively, human TAP1 gene and TAP2 gene are located in different loci of the chromosome 6 band p21.3 (16). TAP gene polymorphism has an influence on peptide selectivity, and mutations in the TAP1 and/or TAP2 genes would produce some nonfunctional proteins that could have a severe impact on the cellular immune system, even leading to genetic diseases, such as the rare bare lymphocyte syndrome (BLS), autoimmune disease and transplantation reaction and tumor (12,17,18). An A-to-G transition of the TAP1 gene at codon 637 would lead to replacement of Asp-637 by glycine (19), and such a replacement may play an important role in the assembly of class I molecules and presentation of endogenous peptides (derived from the nucleus and cytosole) to CD8 (+) T cells.…”

Section: Discussionmentioning

confidence: 99%

Association Study between Hypertension and A/G Polymorphism at Codon 637 of the Transporter Associated with Antigen Processing 1 Gene

Shen

Guo²,

et al. 2007

Hypertens Res

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Splice acceptor site mutation of the transporter associated with antigen processing-1 gene in human bare lymphocyte syndrome

Cited by 54 publications

References 21 publications

HLA-B44 Polymorphisms at Position 116 of the Heavy Chain Influence TAP Complex Binding via an Effect on Peptide Occupancy

HLA-B44 Polymorphisms at Position 116 of the Heavy Chain Influence TAP Complex Binding via an Effect on Peptide Occupancy

Membrane Localization of Transporter Associated with Antigen Processing (TAP)-Like (ABCB9) Visualized in Vivo with a Fluorescence Protein-Fusion Technique

Association Study between Hypertension and A/G Polymorphism at Codon 637 of the Transporter Associated with Antigen Processing 1 Gene

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