Different rates of HLA class I molecule assembly which are determined by amino acid sequence in the α2 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 β₂-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 β2m-associated, sialated form within 30 minutes. Analysis of naturally occurring variants related to HLA-B35 and HLA-B51 localized the region determining assembly efficency to the α2 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.