High frequency of T cells specific for cryptic epitopes in melanoma patients

Rikke Sick Andersen, Sofie Ramskov Andersen, Mads Duus Hjortsø, Rikke Birgitte Lyngaa, Manja Idorn, Tania Maria Kollgard, Özcan Met, Per Thor Straten, Sine Reker Hadrup

Research output: Contribution to journalJournal articleResearchpeer-review


A number of cytotoxic T-cell epitopes are cryptic epitopes generated from non-conventional sources. These include epitopes that are encoded by alternative open reading frames or in generally non-coding genomic regions, such as introns. We have previously observed a frequent recognition of cryptic epitopes by tumor infiltrating lymphocytes isolated from melanoma patients. Here, we show that such cryptic epitopes are more frequently recognized than antigens of the same class encoded by canonical reading frames. Furthermore, we report the presence of T cells specific for three cryptic epitopes encoded in intronic sequences, as a result of incomplete splicing, in the circulation of melanoma patients. One of these epitopes derives from antigen isolated from immunoselected melanoma 2 (AIM2), while the two others are encoded in an alternative open reading frame of an incompletely spliced form of N-acetylglucosaminyl-transferase V (GNT-V) known as NA17-A. We have detected frequent T-cell responses against AIM2 and NA17-A epitopes in the blood of melanoma patients, both prior and after one round of in vitro peptide stimulation, but not in the circulation of healthy individuals and patients with breast or renal carcinoma. In summary, our findings indicate that the T-cell reactivity against AIM2 and NA17-A in the blood of melanoma patients is extensive, suggesting thatsimilar to melan A (also known as MART1)these antigens might be used for immunomonitoring or as model antigens in several clinical and preclinical settings.
Original languageEnglish
Issue number7
Publication statusPublished - 2013
Externally publishedYes


  • Cryptic T-cell epitopes
  • Melanoma
  • CD8 T cells
  • Antigens
  • T-cell reactivity


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