Different rates of HLA class I molecule assembly which are determined by amino acid sequence in the alpha 2 domain.
Assembly of HLA class I molecules was studied using pulse-chase labeling of B-lymphoblastoid cell lines with 35S-methionine, immunoprecipitation with antibodies detecting free or beta 2-microglobulin-associated heavy chain and isoelectric focusing. Marked differences between the products of different class I alleles were noted. HLA-B51 assembled very inefficiently, with considerable free heavy chain still detected in an unsialated form after a four hour chase. The closely related molecule HLA-B35 was in contrast rapidly assembled, all newly synthesized heavy chain being detected in a beta 2m-associated sialated form within 30 minutes. Analysis of naturally occurring variants related to HLA-B35 and HLA-B51 localized the region determining assembly efficiency to the alpha 2 domain, in which these molecules differ at eight amino acid residues. The effect was not due to a linked dominant gene, as both patterns of assembly were observed in a single cell line.
Hill
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Molecular Immunology Group, John Radcliffe Hospital, Oxford, UK.
Takiguchi
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McMichael
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D000595:Amino Acid Sequence; D002461:Cell Line, Transformed; D003429:Cross Reactions; D016521:Electrophoresis, Gel, Pulsed-Field; D000939:Epitopes; D015234:HLA-A Antigens / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D015235:HLA-B Antigens / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007525:Isoelectric Focusing; D008969:Molecular Sequence Data; D011233:Precipitin Tests
D000939:Epitopes; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D007371:Interferon-gamma