title: Expression of a "self-"antigen by human tumor cells enhances tumor antigen-specific CD4(+) T-cell function.
abstract: 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.
authors.affiliation: National Cancer Institute, NIH, Building 10, Room 2B42, Bethesda, MD 20892, USA.
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Touloukian
authors.forename: Wolfgang W
authors.initials: WW
authors.lastname: Leitner
authors.forename: Paul F
authors.initials: PF
authors.lastname: Robbins
authors.forename: Yong F
authors.initials: YF
authors.lastname: Li
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Kang
authors.forename: Rejean
authors.initials: R
authors.lastname: Lapointe
authors.forename: Patrick
authors.initials: P
authors.lastname: Hwu
authors.forename: Steven A
authors.initials: SA
authors.lastname: Rosenberg
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Restifo
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000276:immunology*; D001324:Autoantigens / Q000096:biosynthesis / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology; D059811:HLA-DRB1 Chains; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008545:Melanoma / Q000276:immunology*; D008562:Membrane Glycoproteins; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010088:Oxidoreductases; D011506:Proteins / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D001324:Autoantigens; D018984:Epitopes, T-Lymphocyte; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553505:HLA-DRB1*04:01 antigen; D008562:Membrane Glycoproteins; D011506:Proteins; D010088:Oxidoreductases; C489799:TYRP1 protein, human; C079621:Tyrp1 protein, mouse; C064056:tyrosinase-related protein-1