Polymorphisms of HLA-B: influences on assembly and immunity

The major histocompatibility class I (MHC-I) complex functions in innate and adaptive immunity, mediating surveillance of the subcellular environment. In humans, MHC-I heavy chains are encoded by three genes: the human leukocyte antigen (HLA)-A, HLA-B, and HLA-C. These genes are highly polymorphic, which results in the expression, typically, of six different HLA class I (HLA-I) proteins on the cell surface, and the presentation of diverse peptide antigens to CD8⁺ T cells for broad surveillance against many pathogenic conditions. Recent studies of HLA-B allotypes show that the polymorphisms, not surprisingly, also significantly impact protein folding and assembly pathways. The use of non-canonical assembly routes and the generation of non-canonical HLA-B conformers has consequences for immune receptor interactions and disease therapies.