Recognition of a shared human prostate cancer-associated antigen by nonclassical MHC-restricted CD8+ T cells.
To identify prostate cancer-associated Ags, tumor-reactive T lymphocytes were generated using iterative stimulations of PBMC from a prostate cancer patient with an autologous IFN-gamma-treated carcinoma cell line in the presence of IL-2. A CD8+ T cell line and TCR alphabeta+ T cell clone were isolated that secreted IFN-gamma and TNF-alpha in response to autologous prostate cancer cells but not to autologous fibroblasts or lymphoblastoid cells. However, these T cells recognized several normal and malignant prostate epithelial cell lines without evidence of shared classical HLA molecules. The T cell line and clone also recognized colon cancers, but not melanomas, sarcomas, or lymphomas, suggesting recognition of a shared epithelium-associated Ag presented by nonclassical MHC or MHC-like molecules. Although Ag recognition by T cells was inhibited by mAb against CD8 and the TCR complex (anti-TCR alphabeta, CD3, Vbeta12), it was not inhibited by mAb directed against MHC class Ia or MHC class II molecules. Neither target expression of CD1 molecules nor HLA-G correlated with T cell recognition, but beta2-microglobulin expression was essential. Ag expression was diminished by brefeldin A, lactacystin, and cycloheximide, but not by chloroquine, consistent with an endogenous/cytosolic Ag processed through the classical class I pathway. These results suggest that prostate cancer and colon cancer cells can process and present a shared peptidic Ag to TCR alphabeta+ T cells via a nonclassical MHC I-like molecule yet to be defined.
Housseau
F
F
Surgery Branch, National Cancer Institute, and HLA Laboratory, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA.
Bright
R K
RK
Simonis
T
T
Nishimura
M I
MI
Topalian
S L
SL
D017951:Antigen Presentation; D018949:Antigens, CD1 / Q000276:immunology; D055610:Antigens, CD1d; D000951:Antigens, Neoplasm / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002277:Carcinoma / Q000276:immunology; D002999:Clone Cells; D003110:Colonic Neoplasms / Q000276:immunology; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D006680:HLA Antigens / Q000276:immunology; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D008285:Major Histocompatibility Complex; D008297:Male; D009097:Multienzyme Complexes / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000276:immunology*; D046988:Proteasome Endopeptidase Complex; D016693:Receptors, Antigen, T-Cell, alpha-beta; D001613:beta 2-Microglobulin / Q000276:immunology
D018949:Antigens, CD1; D055610:Antigens, CD1d; D000951:Antigens, Neoplasm; C526877:CD1D protein, human; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D009097:Multienzyme Complexes; D016693:Receptors, Antigen, T-Cell, alpha-beta; D001613:beta 2-Microglobulin; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex