Splice acceptor site mutation of the transporter associated with antigen processing-1 gene in human bare lymphocyte syndrome
Hiroshi Furukawa, … , Keiji Tanaka, Takeo Juji
Hiroshi Furukawa, … , Keiji Tanaka, Takeo Juji
Published March 1, 1999
Citation Information: J Clin Invest. 1999;103(5):755-758. https://doi.org/10.1172/JCI5335.
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Article

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

Abstract

Expression of histocompatibility leukocyte antigen (HLA) class I molecules on the cell surface depends on the heterodimer of the transporter associated with antigen processing 1 and 2 (TAP1 and TAP2), which transport peptides cleaved by proteasome to the class I molecules. Defects in the TAP2 protein have been reported in two families with HLA class I deficiency, the so-called bare lymphocyte syndrome (BLS) type I. We have, to our knowledge, identified for the first time a splice site mutation in the TAP1 gene of another BLS patient. In addition, class I heavy chains (HCs) did not form the normal complex with tapasin in the endoplasmic reticulum (ER) of the cells of our patient.

Authors

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

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Figure 1

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(a) Expression of the mRNA of HLA-A (lanes 1 and 2), HLA-B (lanes 3 and ...
(a) Expression of the mRNA of HLA-A (lanes 1 and 2), HLA-B (lanes 3 and 4), HLA-C (lanes 5 and 6), and G3PDH (lanes 7 and 8) of the lymphocytes of a healthy donor (lanes 1, 3, 5, and 7) and those of KMW (lanes 2, 4, 6, and 8). M represents a molecular weight marker. HLA-A, HLA-B, and HLA-C fragments were amplified by PCR from the cDNA derived from lymphocytes. The PCR products were sequenced by automated sequencing. (b) Consanguineous pedigree and HLA haplotypes of the TSU family. The filled circle represents an affected woman (IV-3, KMW). Partially filled circles (women) and partially filled squares (men) indicate the family members whose samples were analyzed. HLA class I and class II were typed by the sequencing-based typing system as described in Methods, and HLA haplotypes were estimated. (c) Expression of HLA class I molecules on KMW-B2 cells, a B-cell line of KMW, after incubation in the presence or absence of the A24 consensus peptide (A24p, YYEEQHPEL) and β2m. The KMW-B2 cells were preincubated in the presence or absence of 100 mg/ml A24p and 10 mg/ml human β2m for 18 h. KMW-B2 cells or H39 cells, a normal control B-cell line, were stained by FITC-conjugated mouse IgG (shaded histogram) or FITC-conjugated w6/32 and analyzed using the EPICS XL flow cytometer (Coulter Corp.). HLA, histocompatibility leukocyte antigen.