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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(a) Sequences of the TAP1 gene of KMW, the mother (UTT), and a healthy c...
(a) Sequences of the TAP1 gene of KMW, the mother (UTT), and a healthy control. cDNA sequences of the TAP1 gene revealed KMW to be homozygous for TAP1*0102N, an allele with a G deletion in codon 200. Genomic DNA sequencing of the TAP1 gene also revealed a point mutation of G→A on 536 bp in intron 1 of the TAP1*0102N of KMW and the family members (partially filled symbols in Fig. 1b are heterozygous for TAP1*0102N, and only the sequence of the mother is shown). PCR products of the TAP1 gene were sequenced by automated sequencing as described in Methods. (b) Sequences of the TAP1*0101 and TAP1*0102N. G was substituted to A on 536 bp in intron 1 of the TAP1*0102N, which resulted in an altered splice acceptor site and deletion of G in codon 200 of mRNA. This deletion caused a frameshift and resulted in the premature appearance of a stop codon at 228 and the synthesis of a truncated TAP1 protein. (GenBank accession numbers: TAP1*0102N cDNA sequence, AB012644; TAP1*0102N genomic sequence, AB012645.) TAP, transporter associated with antigen processing.