Melan-A/MART-1 sub(51-73) represents an immunogenic HLA-DR4-restricted epitope recognized by melanoma-reactive CD4 super(+) T cells

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 97; no. 1; pp. 400 - 405
• Main Authors: Zarour, H M, Kirkwood, J M, Kierstead, L S, Herr, W, Brusic, V, Slingluff Jr, CL, Sidney, J, Sette, A, Storkus, W J
• Format: Journal Article
• Language: English
• Published: 04.01.2000
• Subjects: CD4 antigen; histocompatibility antigen HLA; Melan-A antigen
• ISSN: 0027-8424
• DOI: 10.1073/pnas.97.1.400

The human Melan-A/MART-1 gene encodes an HLA-A2-restricted peptide epitope recognized by melanoma- reactive CD8 super(+) cytotoxic T lymphocytes. Here we report that this gene also encodes at least one HLA-DR4-presented peptide recognized by CD4 super(+) T cells. The Melan-A/MART-1 sub(51-73) peptide was able to induce the in vitro expansion of specific CD4 super(+) T cells derived from normal DR4 super(+) donors or from DR4 super(+) patients with melanoma when pulsed onto autologous dendritic cells. CD4 super(+) responder T cells specifically produced IFN- gamma in response to, and also lysed, T2.DR4 cells pulsed with the Melan-A/MART-1 sub(51- 73) peptide and DR4 super(+) melanoma target cells naturally expressing the Melan-A/MART-1 gene product. Interestingly, CD4 super(+) T cell immunoreactivity against the Melan-A/MART- 1 sub(51-73) peptide typically coexisted with a high frequency of anti-Melan-A/MART-1 sub(27-35) reactive CD8 super(+) T cells in freshly isolated blood harvested from HLA-A2 super(+)/DR4 super(+) patients with melanoma. Taken together, these data support the use of this Melan-A/MART-1 DR4-restricted melanoma epitope in future immunotherapeutic trials designed to generate, augment, and quantitate specific CD4 super(+) T cell responses against melanoma in vivo.