High frequency of T cells specific for cryptic epitopes in melanoma patients
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High frequency of T cells specific for cryptic epitopes in melanoma patients. / Andersen, Rikke Sick; Andersen, Sofie Ramskov; Hjortsø, Mads Duus; Lyngaa, Rikke; Idorn, Manja; Køllgård, Tania Maria; Met, Özcan; Straten, Perthor; Hadrup, Sine Reker.
I: OncoImmunology, Bind 2, Nr. 7, e25374, 2013.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - High frequency of T cells specific for cryptic epitopes in melanoma patients
AU - Andersen, Rikke Sick
AU - Andersen, Sofie Ramskov
AU - Hjortsø, Mads Duus
AU - Lyngaa, Rikke
AU - Idorn, Manja
AU - Køllgård, Tania Maria
AU - Met, Özcan
AU - Straten, Perthor
AU - Hadrup, Sine Reker
PY - 2013
Y1 - 2013
N2 - 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 that-similar to melan A (also known as MART 1)-these antigens might be used for immunomonitoring or as model antigens in several clinicaland preclinical settings.
AB - 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 that-similar to melan A (also known as MART 1)-these antigens might be used for immunomonitoring or as model antigens in several clinicaland preclinical settings.
KW - Antigens
KW - CD8 T cells
KW - Cryptic T-cell epitopes
KW - Melanoma
KW - T-cell reactivity
UR - http://www.scopus.com/inward/record.url?scp=84886945647&partnerID=8YFLogxK
U2 - 10.4161/onci.25374
DO - 10.4161/onci.25374
M3 - Journal article
AN - SCOPUS:84886945647
VL - 2
JO - OncoImmunology
JF - OncoImmunology
SN - 2162-4011
IS - 7
M1 - e25374
ER -
ID: 176376056