Allele-specific expression of the cytoplasmic exon of HLA-DQB1 gene.
The beta chain of the HLA-DQ molecule is shorter by eight amino acid residues than other major histocompatibility complex class II beta chains due to elimination of the fifth exon coding for part of the cytoplasmic domain. This elimination is caused by one base substitution in the splice acceptor site of the exon. We found that two HLA-DQB1 alleles, DQB1*0503 and DQB1*0601, did not have this substitution, and the exon was utilized in these two alleles. However, two forms of HLA-DQB mRNA, with or without exon 5, were generated in Epstein-Barr virus-transformed cell lines homozygous for DQB1*0503 or DQB1*0601, indicating alternative mRNA splicing. The alternative splicing of DQB1*0601 mRNA was also found in peripheral blood lymphocytes and L cell transfectants. To investigate the functional relevance of the allele-specific long cytoplasmic tail of HLA-DQ beta chain, we developed three types of L cell transfectants expressing exclusively the HLA-DQw6 molecules with short cytoplasmic tail, long cytoplasmic tail, or both forms of the beta chain, and used them as antigen presenting cells for streptococcal cell wall antigen-specific T cell lines. These three types of transfectants could function almost equally well as antigen presenting cells. It was thus demonstrated that both forms of HLA-DQ beta chain, with or without eight amino acid residues coded for by the exon 5, can be associated with the HLA-DQ alpha chain, be expressed on the cell surface, and function as restriction molecules in antigen recognition by the CD4+ T cells.
Senju
S
S
Department of Genetics, Kyushu University, Fukuoka, Japan.
Kimura
A
A
Yasunami
M
M
Kamikawaji
N
N
Yoshizumi
H
H
Nishimura
Y
Y
Sasazuki
T
T
D000483:Alleles; D001483:Base Sequence; D002461:Cell Line, Transformed; D003593:Cytoplasm / Q000276:immunology*; D005091:Exons / Q000235:genetics*; D015870:Gene Expression; D006683:HLA-DQ Antigens / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D014162:Transfection
D006683:HLA-DQ Antigens