Human T cell responses to endogenously presented HLA-A*0201 restricted peptides of Simian virus 40 large T antigen.
Presence of the simian virus 40 (SV40) has recently been demonstrated in a relatively high percentage of human mesotheliomas and it is associated with the development of these malignancies in pleural cavities. Therefore, we have initiated a study to identify candidate peptides presented by the human HLA-A*0201 molecule for vaccination approaches against SV40 and monitoring of SV40 directed human immune responses. Initial screening of SV40 large T (Tag) domains required for transformation of cells for HLA-A*0201 binding motifs revealed ten possible binding peptides. Screening of these candidate peptides showed that seven of the ten peptides could bind and stabilize HLA-A*0201 molecules. In an in vitro immunization assay the two peptides with the highest binding affinity for HLA-A*0201, Tag aa 396-405 and aa 577-585, were tested for their ability to induce peptide specific cytotoxic T cells in two healthy donors. One donor developed cytotoxic T cells against Tag aa 396-405 and in T cell cultures of both donors Tag aa 577-585 specific T cells were initiated. The T cells against Tag aa 577-585 not only recognized and killed peptide pulsed cells, but, most importantly, SV40 transformed human mesothelial cells. This is the first demonstration of the induction of SV40 specific human cytotoxic T lymphocytes that recognize endogenously processed peptides from SV40. This peptide identification study opens the possibility to investigate immune responses against SV40 in mesothelioma patients and in individuals exposed to SV40.
Velders
M P
MP
Cancer Immunology Program, Cardinal Bernardin Cancer Center, Loyola University Chicago, Maywood, Illinois 60153, USA.
Macedo
M F
MF
Provenzano
M
M
Elmishad
A G
AG
Holzhütter
H G
HG
Carbone
M
M
Kast
W M
WM
D000957:Antigens, Viral, Tumor / Q000737:chemistry / Q000276:immunology*; D001665:Binding Sites; D002460:Cell Line; D002472:Cell Transformation, Viral; D004848:Epithelium / Q000276:immunology* / Q000821:virology*; D015234:HLA-A Antigens / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D010455:Peptides / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology; D013539:Simian virus 40 / Q000276:immunology* / Q000472:pathogenicity; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*; D014611:Vaccination
D000957:Antigens, Viral, Tumor; D015234:HLA-A Antigens; D010455:Peptides