Peptide Presentation by Different HLA-Class I Molecules During Viral Infection (APP2P.106)

Abstract Class I Human Leukocyte Antigens reveal intracellular viruses to the immune system by presenting viral epitopes at the cell surface. In this study we hypothesized that during infection particular HLA class I alleles consistently present more virus-derived peptide ligands to virus-specific CD8+ T cells than do other HLA class I. To test this hypothesis, we infected cells with West Nile virus (WNV) and directly identified and enumerated the virus specific peptides presented by various HLA class I molecules. Cells expressing a number of different HLA-A and HLA-B class I were cultured in bioreactors and infected with WNV. HLA/peptide complexes were harvested from infected and uninfected cells, peptides were eluted from affinity-purified HLA, comparatively mapped by mass spectroscopy, and sequenced. Twenty-four peptides, 20 eluted from HLA-A complexes (HLA-A*02:01, A*01:01, A*11:01 and A*24:02) and 4 from HLA-B complexes (HLA-B*27:05, B*07:02 and B*35:01), were identified as unique to infected cells. Ligands represented different parts of the viral polyprotein demonstrating that peptides sampled by class I HLA are distributed widely throughout the WNV proteome. These data indicate that, in WNV-infected cells, HLA-A present more virus-specific peptides than do HLA-B suggesting a potentially different role for HLA class I loci in developing immune responses that control WNV infection whereby HLA-A is responsible for diverse reactivity and HLA-B leads to more focused immunity.