Quantitating T Cell Cross-Reactivity for Unrelated Peptide Antigens
Ishizuka J., Grebe K., Shenderov E., Peters B., Chen Q., Peng Y., Wang L., Dong T., Pasquetto V., Oseroff C., Sidney J., Hickman H., Cerundolo V., Sette A., Bennink JR., McMichael A., Yewdell JW.
Abstract Quantitating the frequency of T cell cross-reactivity to unrelated peptides is essential to understanding T cell responses in infectious and autoimmune diseases. Here we used 15 mouse or human CD8+ T cell clones (11 antiviral, 4 anti-self) in conjunction with a large library of defined synthetic peptides to examine nearly 30,000 TCR-peptide MHC class I interactions for cross-reactions. We identified a single cross-reaction consisting of an anti-self TCR recognizing a poxvirus peptide at relatively low sensitivity. We failed to identify any cross-reactions between the synthetic peptides in the panel and polyclonal CD8+ T cells raised to viral or alloantigens. These findings provide the best estimate to date of the frequency of T cell cross-reactivity to unrelated peptides (∼1/30,000), explaining why cross-reactions between unrelated pathogens are infrequently encountered and providing a critical parameter for understanding the scope of self-tolerance.