Data from: Selected HLA-B allotypes are resistant to inhibition or deficiency of the transporter associated with antigen processing (TAP)

Major histocompatibility complex class I (MHC-I) molecules present
antigenic peptides to CD8+ T cells, and are also important for natural
killer (NK) cell immune surveillance against infections and cancers. MHC-I
molecules are assembled via a complex assembly pathway in the endoplasmic
reticulum (ER) of cells. Peptides present in the cytosol of cells are
transported into the ER via the transporter associated with antigen
processing (TAP). In the ER, peptides are assembled with MHC-I molecules
via the peptide-loading complex (PLC). Components of the MHC-I assembly
pathway are frequently targeted by viruses, in order to evade host
immunity. Many viruses encode inhibitors of TAP, which is thought to be a
central source of peptides for the assembly of MHC-I molecules. However,
human MHC-I (HLA-I) genes are highly polymorphic, and it is conceivable
that several variants can acquire peptides via TAP-independent pathways,
thereby conferring resistance to pathogen-derived inhibitors of TAP. To
broadly assess TAP-independent expression within the HLA-B locus,
expression levels of 27 frequent HLA-B alleles were tested in cells with
deficiencies in TAP. Approximately 15% of tested HLA-B allotypes are
expressed at relatively high levels on the surface of TAP1 or
TAP2-deficient cells and occur in partially peptide-receptive forms and
Endoglycosidase H sensitive forms on the cell surface. Synergy between
high peptide loading efficiency, broad specificity for peptides prevalent
within unconventional sources and high intrinsic stability of the empty
form allows for deviations from the conventional HLA-I assembly pathway
for some HLA-B*35, HLA-B*57 and HLA-B*15 alleles. Allotypes that display
higher expression in TAP-deficient cells are more resistant to viral TAP
inhibitor-induced HLA-I down-modulation, and HLA-I down-modulation-induced
NK cell activation. Thus, unconventional antigen presentation pathways are
broadly prevalent among HLA-B allotypes, and provide mechanisms to counter
pathogen evasion strategies that target the conventional TAP-dependent
HLA-I assembly pathway.