Antigen presentation of a modified tumor-derived peptide by tumor infiltrating lymphocytes.
CD8+ T-lymphocytes recognize peptides in the context of major histocompatibility complex (MHC) class I antigens. Upon activation, these cells differentiate into effector cytotoxic T lymphocytes (CTL) and no longer require formal antigen presentation by professional antigen presenting cells (APC). Subsequently, any cell expressing MHC class I/cognate peptide can stimulate CTL. Using TIL specific for a melanoma antigen-derived peptide, IMDQVPFSV (g209 2M), we sought to determine whether these CTL could present peptide to each other. Our findings demonstrate that peptide presentation of the g209 2M peptide epitope by TIL is comparable to conventional methods of using T2 cells as APC. We report here that CTL are capable of self-presentation of antigenic peptide to neighboring CTL resulting in IFN-gamma secretion, proliferation, and lysis of peptide-loaded CTL. These results demonstrate that human TIL possess both APC functions as well as cytotoxic functions and that this phenomenon could influence CTL activity elicited by immunotherapy.
Dionne
S O
SO
Department of Microbiology and Immunology, University of Arizona, Tucson, Arizona 85724, USA.
Smith
M H
MH
Marincola
F M
FM
Lake
D F
DF
D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D007114:Immunization; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism; D008545:Melanoma / Q000276:immunology*; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000276:immunology
D000951:Antigens, Neoplasm; D015789:HLA-A2 Antigen; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D014763:Viral Matrix Proteins; C098952:influenza virus membrane protein (58-66); D007371:Interferon-gamma