title: Cytotoxic T lymphocyte responses against melanocytes and melanoma.
abstract: BACKGROUND
  Vitiligo is a common toxicity associated with immunotherapy for melanoma. Cytotoxic T lymphocytes (CTLs) against melanoma commonly target melanoma-associated antigens (MAAs) which are also expressed by melanocytes. To uncouple vitiligo from melanoma destruction, it is important to understand if CTLs can respond against melanoma and melanocytes at different levels.
  
  
  METHODS
  To understand the dichotomous role of MAA-specific CTL, we characterized the functional reactivities of established CTL clones directed to MAAs against melanoma and melanocyte cell lines.
  
  
  RESULTS
  CTL clones generated from melanoma patients were capable of eliciting MHC-restricted, MAA-specific lysis against melanocyte cell lines as well as melanoma cells. Among the tested HLA-A*0201-restricted CTL clones, melanocytes evoked equal to slightly higher degranulation and cytolytic responses as compared to melanoma cells. Moreover, MAA-specific T cells from vaccinated patients responded directly ex vivo to melanoma and melanocytes. Melanoma cells express slightly higher levels of MART-1 and gp100 than melanocytes as measured by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and immunohistochemistry.
  
  
  CONCLUSIONS
  Our data suggest that CTLs respond to melanoma and melanocytes equally in vitro and directly ex vivo.
authors.affiliation: Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Gwendolen Y
authors.initials: GY
authors.lastname: Chang
authors.forename: Holbrook E
authors.initials: HE
authors.lastname: Kohrt
authors.forename: Tor B
authors.initials: TB
authors.lastname: Stuge
authors.forename: Erich J
authors.initials: EJ
authors.lastname: Schwartz
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Weber
authors.forename: Peter P
authors.initials: PP
authors.lastname: Lee
mesh_terms: D019496:Cancer Vaccines / Q000276:immunology; D015550:Cell Degranulation; D045744:Cell Line, Tumor; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D058965:MART-1 Antigen / Q000276:immunology; D008544:Melanocytes / Q000276:immunology*; D008545:Melanoma / Q000276:immunology*; D010455:Peptides / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000502:physiology; D014611:Vaccination
chemical_list: D019496:Cancer Vaccines; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D058965:MART-1 Antigen; D010455:Peptides