TY - JOUR
T1 - Expression of a "self-"antigen by human tumor cells enhances tumor antigen-specific CD4+ T-cell function
AU - Touloukian, Christopher E.
AU - Leitner, Wolfgang W.
AU - Robbins, Paul F.
AU - Li, Yong F.
AU - Kang, Xiaoqiang
AU - Lapointe, Rejean
AU - Hwu, Patrick
AU - Rosenberg, Steven A.
AU - Restifo, Nicholas P.
PY - 2002/9/15
Y1 - 2002/9/15
N2 - CD4+ T cells can recognize "self" tumor antigens, but the impact of tumor cell expression of self-antigens on CD4+ T-cell function in humans is unknown. Here, we identify a new epitope (ISPNSVFSQWRVVCDSLEDYD) derived from tyrosinase-related protein-1 (TRP-1) using a predictive algorithm and mice transgenic for a chimeric HLA-DRB1*0401 molecule. We then compared the functions of TRP-1-epitope-specific, CD4+ T-cell responses in normal healthy individuals to those found in patients with metastatic malignant melanoma. Surprisingly, we found that tumor-bearing patients had significantly higher levels of TRP-1-specific, CD4+ T-cell function than healthy volunteers as measured ex vivo. Thus, the net effect of "self" antigen expression by tumor cells was the enhancement of tumor antigen-specific CD4+ T-cell function, rather than immunosuppression. These findings indicate that antigens expressed by malignant melanoma cells can partially activate CD4+ T lymphocytes.
AB - CD4+ T cells can recognize "self" tumor antigens, but the impact of tumor cell expression of self-antigens on CD4+ T-cell function in humans is unknown. Here, we identify a new epitope (ISPNSVFSQWRVVCDSLEDYD) derived from tyrosinase-related protein-1 (TRP-1) using a predictive algorithm and mice transgenic for a chimeric HLA-DRB1*0401 molecule. We then compared the functions of TRP-1-epitope-specific, CD4+ T-cell responses in normal healthy individuals to those found in patients with metastatic malignant melanoma. Surprisingly, we found that tumor-bearing patients had significantly higher levels of TRP-1-specific, CD4+ T-cell function than healthy volunteers as measured ex vivo. Thus, the net effect of "self" antigen expression by tumor cells was the enhancement of tumor antigen-specific CD4+ T-cell function, rather than immunosuppression. These findings indicate that antigens expressed by malignant melanoma cells can partially activate CD4+ T lymphocytes.
UR - http://www.scopus.com/inward/record.url?scp=0037105742&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037105742&partnerID=8YFLogxK
M3 - Article
C2 - 12234976
AN - SCOPUS:0037105742
SN - 0008-5472
VL - 62
SP - 5144
EP - 5147
JO - Cancer Research
JF - Cancer Research
IS - 18
ER -