Data for: Endo-lysosomal assembly variations among Human Leukocyte Antigen class I (HLA-I) allotypes

The extreme polymorphisms of HLA-I proteins enable the presentation of
diverse peptides to cytotoxic T lymphocytes (CTL). The canonical
endoplasmic reticulum (ER) HLA-I assembly pathway enables presentation of
cytosolic peptides, but effective intracellular surveillance requires
multi-compartmental antigen sampling. Endo-lysosomes are generally sites
of HLA class II assembly, but human monocytes and monocyte-derived
dendritic cells (moDCs) also contain significant reserves of
endo-lysosomal HLA-I molecules. We hypothesized variable influences of
HLA-I polymorphisms upon outcomes of endo-lysosomal trafficking, as the
stabilities and peptide occupancies of cell surface HLA-I are variable.
Consistent with this model, when the endo-lysosomal pH of moDCs is
disrupted, HLA-B allotypes display varying propensities for reductions in
surface expression, with HLA-B*08:01 or HLA-B*35:01 being among the most
resistant or sensitive respectively, among eight tested HLA-B allotypes.
Perturbations of moDC endo-lysosomal pH result in redistribution of
HLA-B*35:01, but not HLA-B*08:01, to LAMP1+ compartments and increase
HLA-B*35:01 peptide receptivity. These findings reveal the intersection of
the vacuolar cross-presentation pathway with a constitutive assembly
pathway for some HLA-B allotypes. Notably, cross-presentation of epitopes
derived from two soluble antigens was also more efficient for B*35:01
compared to B*08:01, even when matched for T cell response sensitivity,
and more affected by cathepsin inhibition. Thus, HLA-I polymorphisms
dictate the degree of endo-lysosomal assembly, which can supplement ER
assembly for constitutive HLA-I expression and increase the efficiency of
cross-presentation.