HLA-independent heterogeneity of CD8(+) T cell responses to MAGE-3, Melan-A/MART-1, gp100, tyrosinase, MC1R, and TRP-2 in vaccine-treated melanoma patients

An important element in melanoma vaccine construction is to identify peptid es from melanoma-associated Ags that have immunogenic potential in humans a nd are recognized by CD8(+) T cells in vivo. To identify such peptides, we evaluated HLA-A*02(+) melanoma patients immunized to a polyvalent vaccine c ontaining multiple Ags, including MAGE-3, Melan-A/MART-1, gp100, tyrosinase , melanocortin receptor (MC1R), and dopachrome tautomerase (TRP-2), Using a filter spot assay, we measured peripheral blood CD8(+) T cell responses, b efore and after immunization, to a panel of 45 HLA-A*0201-restricted peptid es derived from these Ags, The peptides mere selected for immunogenic poten tial based on their strong binding affinity in vitro to HLA-A*0201, Vaccine treatment induced peptide-specific CD8(+) T cell responses to 22 (47.8%) o f the peptides, The most striking finding was the HLA-independent heterogen eity of responses to both peptides and Ags, All responding patients reacted to different combination of peptides and Ags even though the responding pa tients were all A*0201(+) and the peptides were all A*0201-restricted. From 9 to 27% of patients developed a CD8(+) T cell response to at least one pe ptide from each Ag, but no more than 3 (14%) reacted to the same peptide fr om, tbe same Ag, This heterogeneity of responses to individual peptides and Ags in patients with the same haplotype points to the need to construct va ccines of multiple peptides or Ags to maximize the proportion of responding patients.