Revelation of a cryptic major histocompatibility complex class II-restricted tumor epitope in a novel RNA-processing enzyme

Suzanne L. Topalian, Monica I. Gonzales, Yvona Ward, Xiang Wang, Rong Fu Wang

Research output: Contribution to journalArticlepeer-review

Abstract

CD4+ T-cell responses against human tumor antigens are a potentially critical component of the antitumor immune response. Molecular methods have been devised for rapidly identifying MHC class II-restricted tumor antigens and elucidating the recognized epitopes. We describe here the identification of neo-poly(A) polymerase (neo-PAP), a novel RNA processing enzyme overexpressed in a variety of human cancers, by screening a melanoma-derived invariant chain fusion cDNA library with tumor-reactive CD4+ T lymphocytes. A cryptic nonmutated HLA-DRβ1*0701-restricted neo-PAP epitope was processed through the endogenous MHC class II pathway. A unique point mutation effected a nonconservative substitution of a leucine for a proline residue at a structurally important site in neo-PAP that was remote from the recognized peptide, revealing a normally silent epitope for immune recognition. Genetic aberrations such as the described point mutation can have unexpected immunological consequences, in this case leading to immune recognition of a distant normal self epitope.

Original languageEnglish (US)
Pages (from-to)5505-5509
Number of pages5
JournalCancer Research
Volume62
Issue number19
StatePublished - Oct 1 2002
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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