Antigens derived from melanocyte differentiation proteins: self-tolerance, autoimmunity, and use for cancer immunotherapy.
A large set of peptide antigens presented by class I major histocompatibility complex (MHC) molecules on human and murine melanomas and recognized by CD8+ T cells have been defined. These peptides represent attractive candidates for the development of therapeutic and/or prophylactic approaches to treat this cancer. However, the majority of the peptides that are presented by multiple tumors and recognized by T cells from multiple patients arise from proteins that are also expressed in normal melanocytes. It is expected that immune responses to such peptides will be compromised by self-tolerance or, alternatively, that stimulation of effective immune responses will be accompanied by autoimmune vitiligo. In this review, we describe a preclinical model to evaluate these issues and recent data to suggest that tolerance can be overcome to generate effective antitumor responses. This model also allows the rapid and systematic examination of parameters for the effective use of synthetic peptide vaccines.
Engelhard
Victor H
VH
Carter Immunology Center and Department of Microbiology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA. vhe@virginia.edu
Bullock
Timothy N J
TN
Colella
Teresa A
TA
Sheasley
Stacey L
SL
Mullins
David W
DW
D000417:Albinism / Q000276:immunology; D000818:Animals; D017951:Antigen Presentation; D000943:Antigens, Differentiation / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use; D006801:Humans; D007167:Immunotherapy; D016219:Immunotherapy, Adoptive; D008544:Melanocytes / Q000276:immunology*; D008545:Melanoma / Q000276:immunology / Q000517:prevention & control / Q000628:therapy; D008546:Melanoma, Experimental / Q000276:immunology / Q000628:therapy; D051379:Mice; D008822:Mice, Transgenic; D014442:Monophenol Monooxygenase / Q000737:chemistry / Q000276:immunology; D009363:Neoplasm Proteins / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy; D010446:Peptide Fragments / Q000276:immunology; D017634:Self Tolerance / Q000276:immunology*; D013045:Species Specificity; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000637:transplantation; D022223:Vaccines, Subunit / Q000276:immunology / Q000627:therapeutic use; D014820:Vitiligo / Q000209:etiology / Q000276:immunology
D000943:Antigens, Differentiation; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D022223:Vaccines, Subunit; D014442:Monophenol Monooxygenase