Amino acid substitutions in the melanoma antigen recognized by T cell 1 peptide modulate cytokine responses in melanoma-specific T cells.
Single amino acid substitutions in melanoma-associated peptides dramatically enhance T-cell cytotoxicity against target cells presenting the modified peptides (often referred to as heteroclitic peptides). The authors tried to determine whether peptide modifications influence other aspects of T-cell immunity toward malignant melanoma. A heteroclitic peptide, E26F, with an E to F substitution in melanoma antigen recognized by T cell 1 (MART-1)26-35, triggers an enhanced tyrosine phosphorylation response when compared with the native- and other-modified MART-1 peptides. Similarly, the E26F peptide enhances the production of mRNA for interleukin (IL)-5, IL-10, IL-13, IL-15, and interferon-gamma and significantly enhances release of IL-13 and IL-10 from anti-MART-1 cytotoxic T cells. Another heteroclitic peptide, 1L, with an A to L substitution in MART-1(27-35), also enhances the tyrosine phosphorylation response in anti-MART-1 cytotoxic CD8+ T cells. Yet, 1L does not enhance the production of T helper cell type 2-like cytokines (IL-10 and IL-13). Together these data show that minor amino acid modifications of immunodominant melanoma peptides profoundly influence the cytokine response in melanoma-specific T cells.
Institute of Medical Microbiology and Immunology, University of Copenhagen, Denmark.
M B
MB
Nielsen
A F
AF
Kirkin
D
D
Loftus
M H
MH
Nissen
L
L
Rivoltini
J
J
Zeuthen
C
C
Geisler
N
N
Odum
D019943:Amino Acid Substitution; D016207:Cytokines / Q000096:biosynthesis*; D000939:Epitopes / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis; D018793:Interleukin-13 / Q000096:biosynthesis; D009363:Neoplasm Proteins / Q000235:genetics* / Q000276:immunology*; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014407:Tumor Cells, Cultured
D016207:Cytokines; D000939:Epitopes; D016056:Immunodominant Epitopes; D018793:Interleukin-13; C105787:MART-1-Melan-A(27-35) epitope; D009363:Neoplasm Proteins; D016753:Interleukin-10; D019000:Phosphotyrosine