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Impaired assembly and transport of HLA‐A and ‐B antigens in a mutant TxB cell hybrid.
Author(s) -
Salter R.D.,
Cresswell P.
Publication year - 1986
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/j.1460-2075.1986.tb04307.x
Subject(s) - biology , human leukocyte antigen , antigen , beta 2 microglobulin , antigen processing , major histocompatibility complex , microbiology and biotechnology , gene , northern blot , mhc class i , mutant , locus (genetics) , genetics , gene expression , immunology
Biosynthesis of HLA class I antigens has been studied in a variant B‐LCLxT‐LCL hybrid, 174XCEM.T2. This cell line encodes HLA‐A2 and ‐B5, but expresses only small amounts of A2 antigen and undetectable B5 antigen at the cell surface due to a mutation inactivating a trans‐acting regulatory gene encoded within the class II region of the human major histocompatibility complex. Northern blot analysis with HLA‐A‐ and HLA‐B‐specific probes shows that 174XCEM.T2 synthesizes quantities of A and B locus mRNA comparable with its class I antigen‐positive parent cell line. Immune precipitation studies indicate that 174XCEM.T2 synthesizes normal HLA heavy chains and beta 2‐microglobulin which fail to form dimers. The heavy chains are N‐glycosylated normally, but processing of the glycan to the complex form does not occur. In addition, free heavy chains in this cell line are not phosphorylated. Thus, the majority of class I heavy chains in 174XCEM.T2 do not combine with beta 2‐microglobulin, and are not processed or transported to the cell surface. As both subunits are synthesized in normal amounts, we propose that an additional molecule absent from 174XCEM.T2 and encoded by an HLA‐linked gene is necessary for efficient assembly of class I antigen subunits.