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

TY - JOUR

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

SN - 2162-4011

VL - 2

JO - OncoImmunology

JF - OncoImmunology

IS - 7

M1 - e25374

ER -