How frequently are predicted peptides actually recognized by CD8 cells?

Area of Science:

• Immunology
• Virology
• Computational Biology

Background:

• Antigen-specific CD8 T-cell detection often uses predicted peptides binding to HLA Class I molecules.
• Well-defined immunogenic peptides exist for Cytomegalovirus, Epstein-barr virus, and Influenza virus (CEF peptides).

Purpose of the Study:

• To evaluate the accuracy of predicted peptide recognition for detecting CD8 T-cell responses in healthy donors.
• To compare the effectiveness of individual peptides versus peptide pools for immune monitoring.

Main Methods:

• High-resolution HLA-typing of 42 healthy human donors.
• Testing CD8 T-cell responses against 32 individual CEF peptides based on binding predictions.
• Analyzing frequency and occurrence of detected T-cell responses.

Main Results:

• Only 15% of predicted CD8 T-cell responses were high-frequency; 49% were undetectable.
• Individual CEF peptides were recognized unpredictably in 57 cases.
• Response frequency to one peptide did not correlate with responses to other determinants of the same antigen.

Conclusions:

• Reliance on single predicted peptides offers an inaccurate assessment of antigen-specific CD8 T-cell immunity.
• Using peptide pools is strongly recommended for accurate immune monitoring and assessment of T-cell responses.