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New T-cell epitope math

Posttranslational protein fragment splicing can generate many more epitopes than thought

David Secko(dmsecko@interchange.ubc.ca)

When predicting T-cell epitopes from a protein—a useful technique for cancer and vaccine research—it has been generally thought that theoretically chopping the proteins into eight- to ten-amino acid fragments would give all its possible epitopes. But in the January 15 Nature, Ken-ichi Hanada and colleagues from the National Institutes of Health have discovered that the posttranslational splicing of protein fragments can generate new epitope variants and suggest that there are far more possible epitopes than previously thought (Nature, 427:252-256, January 15, 2004).

“We started by looking for proteins on kidney cancer cells that would be recognized by the immune system,” said James C. Yang, principal investigator of the study, who together with Hanada and colleagues had previously cloned a human T cell (C2 cytotoxic T-lymphocytes, or CTLs) that killed cancer cells overexpressing fibroblast growth factor-5 (FGF-5).

“[We] wanted to proceed to find the specific nine...

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