HLA class I molecules consistently present internal influenza epitopes

Area of Science:

• Immunology
• Virology
• Proteomics

Background:

• Cytotoxic T lymphocytes (CTL) are crucial for controlling influenza virus infections by recognizing viral epitopes presented on MHC class I molecules.
• The precise number and origin of viral epitopes presented by HLA class I molecules on infected cells remain largely unknown.

Purpose of the Study:

• To elucidate the repertoire of influenza virus-derived peptides presented by the human MHC class I molecule HLA-B*0702.
• To identify the specific viral proteins and epitopes recognized by CTL following influenza infection.

Main Methods:

• Direct identification of HLA-B*0702-presented viral peptides using mass spectrometry after influenza infection of cells expressing soluble HLA-B*0702.
• Isolation and characterization of peptide ligands from infected cells.
• Assessment of CTL recognition of identified viral peptides using HLA-B*0702 transgenic mice.

Main Results:

• HLA-B*0702 presented 3-6 viral ligands per influenza strain.
• Internal viral proteins, nucleoprotein (NP) and polymerase subunit PB1, yielded consistently presented peptides (NP(418-426), NP(473-481), PB1(329-337)).
• Ligands from hemagglutinin (HA) and matrix protein (M1) were presented intermittently, and only internal protein-derived peptides elicited significant CTL responses in mice.

Conclusions:

• A limited set of internal viral protein-derived peptides are consistently presented by HLA class I molecules during influenza infection.
• CTL primarily recognize these consistently presented internal viral epitopes, suggesting a focused immune response against conserved viral components.