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. 1985 May;4(5):1205–1210. doi: 10.1002/j.1460-2075.1985.tb03761.x

Unusual RNA splicing generates a secreted form of HLA-A2 in a mutagenized B lymphoblastoid cell line.

M S Krangel
PMCID: PMC554325  PMID: 3874058

Abstract

Human class I major histocompatibility antigens (HLA-A, -B and -C) are integral membrane glycoprotein heterodimers. A mutagenized B lymphoblastoid cell line has been previously shown to synthesize two forms of the HLA-A2 antigen; a minor form which remains cell-associated at all times, and an abundant form, which is secreted. The present study reports the isolation of cDNA clones for both the wild-type HLA-A2 molecule synthesized by the parent cell line and the secreted molecule synthesized by the mutant cell line. A comparison of their structures indicates that transcripts encoding the mutant HLA-A2 molecule lack the 117 nucleotides encoded by exon five of the HLA-A2 gene. This exon encodes the hydrophobic amino acids which are thought to anchor the polypeptide in the plasma membrane. This result supports an alternative splicing model to explain the phenotype of the mutant cell line. Further, it implies that information encoded in exon five is essential for anchoring class I antigens in the plasma membrane. The potential for a similar splicing mechanism to generate soluble forms of class I antigens in vivo is discussed.

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