gp 100/pmel17 and tyrosinase encode multiple epitopes recognized by Th1-type CD4+ T cells

L. S. Kierstead, E. Ranieri, W. Olson, V. Brusic, J. Sidney, A. Sette, Y. L. Kasamon, C. L. Slingluff, J. M. Kirkwood, W. J. Storkus

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

CD4+ T cells modulate the magnitude and durability of CTL responses in vivo, and may serve as effector cells in the tumour microenvironment. In order to identify the tumour epitopes recognized by tumour-reactive human CD4+ T cells, we combined the use of an HLA-DR4/peptide binding algorithm with an IFN-γ ELISPOT assay. Two known and three novel CD4+ T cell epitopes derived from the gp 100/pmel17 and tyrosinase melanocyte-associated antigens were confirmed or identified. Of major interest, we determined that freshly-isolated PBMC frequencies of Th1-type CD4+ T recognizing these peptides are frequently elevated in HLA-DR4+ melanoma patients (but not normal donors) that are currently disease-free as a result of therapeutic intervention. Epitope-specific CD4+ T cells from normal DR4+ donors could be induced, however, after in vitro stimulation with autologous dendritic cell pulsed with antigens (peptides or antigen-positive melanoma lysates) or infected with recombinant vaccinia virus encoding the relevant antigen. Peptide-reactive CD4+ T cells also recognized HLA-DR4+ melanoma cell lines that constitutively express the relevant antigen. Based on these data, these epitopes may serve as potent vaccine components to promote clinically-relevant Th1-type CD4+ T cell effector function in situ.

Original languageEnglish
Pages (from-to)1738-1745
Number of pages8
JournalBritish Journal of Cancer
Volume85
Issue number11
DOIs
Publication statusPublished - Nov 30 2001
Externally publishedYes

Fingerprint

Monophenol Monooxygenase
Epitopes
HLA-DR4 Antigen
T-Lymphocytes
Antigens
Peptides
Melanoma
Tissue Donors
Melanoma-Specific Antigens
Peptide T
Enzyme-Linked Immunospot Assay
T-Lymphocyte Epitopes
Tumor Microenvironment
Vaccinia virus
Melanocytes
Dendritic Cells
Neoplasms
Vaccines
Cell Line

Keywords

  • ELISPOT
  • gp 100/pmel17
  • Helper T cells
  • Melanoma
  • Tyrosinase
  • Vaccine

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Kierstead, L. S., Ranieri, E., Olson, W., Brusic, V., Sidney, J., Sette, A., ... Storkus, W. J. (2001). gp 100/pmel17 and tyrosinase encode multiple epitopes recognized by Th1-type CD4+ T cells. British Journal of Cancer, 85(11), 1738-1745. https://doi.org/10.1054/bjoc.2001.2160

gp 100/pmel17 and tyrosinase encode multiple epitopes recognized by Th1-type CD4+ T cells. / Kierstead, L. S.; Ranieri, E.; Olson, W.; Brusic, V.; Sidney, J.; Sette, A.; Kasamon, Y. L.; Slingluff, C. L.; Kirkwood, J. M.; Storkus, W. J.

In: British Journal of Cancer, Vol. 85, No. 11, 30.11.2001, p. 1738-1745.

Research output: Contribution to journalArticle

Kierstead, LS, Ranieri, E, Olson, W, Brusic, V, Sidney, J, Sette, A, Kasamon, YL, Slingluff, CL, Kirkwood, JM & Storkus, WJ 2001, 'gp 100/pmel17 and tyrosinase encode multiple epitopes recognized by Th1-type CD4+ T cells', British Journal of Cancer, vol. 85, no. 11, pp. 1738-1745. https://doi.org/10.1054/bjoc.2001.2160
Kierstead LS, Ranieri E, Olson W, Brusic V, Sidney J, Sette A et al. gp 100/pmel17 and tyrosinase encode multiple epitopes recognized by Th1-type CD4+ T cells. British Journal of Cancer. 2001 Nov 30;85(11):1738-1745. https://doi.org/10.1054/bjoc.2001.2160
Kierstead, L. S. ; Ranieri, E. ; Olson, W. ; Brusic, V. ; Sidney, J. ; Sette, A. ; Kasamon, Y. L. ; Slingluff, C. L. ; Kirkwood, J. M. ; Storkus, W. J. / gp 100/pmel17 and tyrosinase encode multiple epitopes recognized by Th1-type CD4+ T cells. In: British Journal of Cancer. 2001 ; Vol. 85, No. 11. pp. 1738-1745.
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