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 dramaticall y 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)(26-3 5) triggers an enhanced tyrosine phosphorylation response when compared wit h the native- and other-modified MART-1 peptides. Similarly, the E26F pepti de 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 I L-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 pho sphorylation 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 a nd 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.