Transporter associated with antigen processing (TAP) dependencies and cell surface peptide occupancies of HLA-B allotypes

Abstract

Abstract Human leukocyte antigens (HLA) class I molecules comprise a highly polymorphic heavy chain complexed to beta2-microglobulin (β2m). The heterodimers bind and display short peptides on the cell surface for intracellular surveillance by cytotoxic T cells. Peptides that assemble with HLA class I molecules are typically derived from the cytosol of cells, whereas the assembly of HLA class I occurs within the ER lumen. The transporter associated with antigen processing (TAP) is essential for peptide transport from the cytosol into the ER. In this study we showed that frequently occurring HLA-B variants display distinct patterns of TAP dependencies. Some HLA-B allotypes are detectable at significant levels in TAP-deficient and TAP-inhibited cells. Such allotypes are predominantly peptide-occupied in TAP-sufficient cells, but display higher percentages of empty protein in cells with inhibited or dysfunctional forms of TAP. TAP activity is known to be blocked by many viral proteins and in some cancers. Our findings indicate TAP dependency-influenced variations in cell surface expression and peptide occupancies of HLA-B allotypes under pathoglocical conditions.