Characterization of Melan-A reactive memory CD8+ T cells in a healthy donor.
Melan-A specific CD8+ T cells are thought to play an important role against the development of melanoma. Their in vivo expansion is often observed with advanced disease. In recent years, low levels of Melan-A reactive CD8+ T cells have also been found in HLA-A2 healthy donors, but these cells harbor naive characteristics and are thought to be mostly cross-reactive for the Melan-A antigen. Here, we report on a large population of CD8+ T cells reactive for the Melan-A antigen, identified in one donor with no evidence of melanoma. Interestingly, this population is oligoclonal and displays a clear memory phenotype. However, a detailed study of these cells indicated that they are unlikely to be directly specific for melanoma, so that their in vivo expansion may have been driven by an exogenous antigen. Screening of a Melan-A cross-reactive peptide library suggested that these cells may be specific for an epitope derived from a Mycobacterium protein, which would provide a further example of CD8+ T cell cross-reactivity between a pathogen antigen and a tumor antigen. Finally, we discuss potential perspectives regarding the role of such cells in heterologous immunity, by influencing the balance between protective immunity and pathology, e.g. in the case of melanoma development.
Multidisciplinary Oncology Center, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
Verena
V
Voelter
Nathalie
N
Rufer
Severine
S
Reynard
Gilbert
G
Greub
Roger
R
Brookes
Philippe
P
Guillaume
Frederic
F
Grosjean
Theres
T
Fagerberg
Olivier
O
Michelin
Sarah
S
Rowland-Jones
Clemencia
C
Pinilla
Serge
S
Leyvraz
Pedro
P
Romero
Victor
V
Appay
D000942:Antigens, Bacterial / Q000276:immunology / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000276:immunology* / Q000627:therapeutic use; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D019496:Cancer Vaccines / Q000627:therapeutic use; D002478:Cells, Cultured; D002999:Clone Cells; D045142:Cross-Priming / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D058965:MART-1 Antigen; D008545:Melanoma / Q000276:immunology / Q000473:pathology / Q000628:therapy; D009169:Mycobacterium tuberculosis; D009363:Neoplasm Proteins / Q000737:chemistry / Q000276:immunology* / Q000627:therapeutic use; D010455:Peptides / Q000737:chemistry / Q000276:immunology* / Q000627:therapeutic use; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000276:immunology*
D000942:Antigens, Bacterial; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D058965:MART-1 Antigen; C548667:MLANA protein, human; D009363:Neoplasm Proteins; D010455:Peptides