Tumour-specific MHC-class-II-restricted responses after in vitro sensitization to synthetic peptides corresponding to gp100 and Annexin II eluted from melanoma cells.
In a search for potentially tumour-specific MHC-class-II-restricted antigens, the immunogenicity of endogenous peptides that had been eluted from HLA-DR molecules of the human melanoma cell line FM3 (HLA-DRB1*02x, DRB1*0401) was tested in vitro. Two 16-mers representing gp100 positions 44-59, and annexin II positions 208-223 bound well to isolated DRB1*0401 molecules and are discussed here. HLA-DR-matched normal donors' T cells were cultured with peptide-pulsed artificial antigen-presenting cells (CHO cells cotransfected with genes for HLA-DRB1*0401 and CD80 and coexpressing high levels of both human molecules). Specific sensitization was achieved against both peptides, as measured in assays of autocrine proliferation and interleukin-2 secretion. Moreover, responses to native autologous melanoma cells but not to autologous B cells were also observed. In view of the expression of fas by the activated T cells and of fas ligand by the melanoma cells, blockade of potential fas/ fas-ligand interactions was undertaken using monoclonal antibodies (mAb). The antagonistic fas-specific mAb M3, but not the fas agonist M33, caused a markedly enhanced T cell response to FM3 cells. These results demonstrate that synthetic peptide antigens are able to sensitize T cells in vitro for effective MHC-class-II-restricted recognition of melanoma cells.
Second Department of Internal Medicine, University of Tübingen Medical School, Germany.
K
K
Li
M
M
Adibzadeh
T
T
Halder
H
H
Kalbacher
S
S
Heinzel
C
C
Müller
J
J
Zeuthen
G
G
Pawelec
D000818:Animals; D017306:Annexin A2 / Q000276:immunology*; D000912:Antibodies, Neoplasm / Q000276:immunology*; D000918:Antibody Specificity; D016466:CHO Cells / Q000378:metabolism; D006224:Cricetinae; D000949:Histocompatibility Antigens Class II / Q000494:pharmacology*; D006801:Humans; D007114:Immunization; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology; D008562:Membrane Glycoproteins / Q000276:immunology*; D009363:Neoplasm Proteins / Q000276:immunology*; D010446:Peptide Fragments / Q000096:biosynthesis; D014407:Tumor Cells, Cultured; D058951:gp100 Melanoma Antigen
D017306:Annexin A2; D000912:Antibodies, Neoplasm; D000949:Histocompatibility Antigens Class II; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C548637:PMEL protein, human; D010446:Peptide Fragments; D058951:gp100 Melanoma Antigen