Multiple HLA class II-restricted melanocyte differentiation antigens are recognized by tumor-infiltrating lymphocytes from a patient with melanoma.
Dramatic clinical responses were observed in patient 888 following the adoptive transfer of autologous tumor-infiltrating lymphocytes (TIL). Previously, extensive analysis of the specificity of class I-restricted T cells from patient 888 TIL has revealed that these T cells recognize a mutated, as well as several nonmutated tumor Ags. Additional studies that were conducted on TIL from patient 888 indicated that they contained CD4-positive T cells that recognized the autologous tumor that had been induced to express HLA class II molecules. Tumor-reactive CD4-positive T cell clones were isolated from TIL and tested for their ability to react with Ags that are recognized by HLA class I-restricted, melanoma-reactive T cells. Using this approach, T cell clones were identified that recognized an epitope expressed in both the tyrosinase-related protein 1 and tyrosinase-related protein 2 Ags in the context of the HLA-DRbeta1*1502 class II gene product. Additional clones were found to recognize an epitope of gp100 in the context of the same HLA-DR restriction element. These observations provide an impetus to develop strategies directed toward generating HLA class II-restricted tumor-reactive T cells.
Robbins
Paul F
PF
Surgery Branch, National Cancer Institute, National Institutes of Health, Building 10, Room 2B42, Bethesda, MD 20892-7502, USA.
El-Gamil
Mona
M
Li
Yong F
YF
Zeng
Gang
G
Dudley
Mark
M
Rosenberg
Steven A
SA
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D000943:Antigens, Differentiation / Q000276:immunology / Q000378:metabolism*; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D019556:COS Cells; D002999:Clone Cells; D003601:Cytotoxicity Tests, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D006680:HLA Antigens / Q000276:immunology / Q000378:metabolism*; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D059811:HLA-DRB1 Chains; D059847:HLA-DRB5 Chains; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007519:Isoantigens / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism; D008544:Melanocytes / Q000276:immunology* / Q000378:metabolism; D008545:Melanoma / Q000276:immunology* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000276:immunology / Q000378:metabolism; D010088:Oxidoreductases; D011506:Proteins / Q000276:immunology / Q000378:metabolism; D014407:Tumor Cells, Cultured; D058951:gp100 Melanoma Antigen
D000943:Antigens, Differentiation; D000951:Antigens, Neoplasm; D018984:Epitopes, T-Lymphocyte; D006680:HLA Antigens; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D059847:HLA-DRB5 Chains; D000949:Histocompatibility Antigens Class II; D007519:Isoantigens; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C548637:PMEL protein, human; D011506:Proteins; D058951:gp100 Melanoma Antigen; D010088:Oxidoreductases; C489799:TYRP1 protein, human; C064056:tyrosinase-related protein-1