Hm. Zarour et al., Melan-A/MART-1(51-73) represents an immunogenic HLA-DR4-restricted epitoperecognized by melanoma-reactive CD4(+) T cells, P NAS US, 97(1), 2000, pp. 400-405
Citations number
28
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
The human Melan-A/MART-1 gene encodes an HLA-A2-restricted peptide epitope
recognized by melanoma-reactive CD8(+) cytotoxic T lymphocytes. Here we rep
ort that this gene also encodes at least one HLA-DR4-presented peptide reco
gnized by CD4(+) T cells. The Melan-A/MART-1(51-73) peptide was able to ind
uce the in vitro expansion of specific CD4(+) T cells derived from normal D
R4(+) donors or from DR4(+) patients with melanoma when pulsed onto autolog
ous dendritic cells. CD4(+) responder T cells specifically produced IFN-gam
ma in response to, and also lysed, T2.DR4 cells pulsed with the Melan-A/MAR
T-1(51-73) peptide and DR4(+) melanoma target cells naturally expressing th
e Melan-A/MART-1 gene product. Interestingly, CD4(+) T cell immunoreactivit
y against the Melan-A/MART-1(51-73) peptide typically coexisted with a high
frequency of anti-Melan-A/MART-1(27-35) reactive CD8(+) T cells in freshly
isolated blood harvested from HLA-A2(+)/DR4(+) patients with melanoma. Tak
en together, these data support the use of this Melan-A/MART-1 DR4-restrict
ed melanoma epitope in future immunotherapeutic trials designed to generate
, augment, and quantitate specific CD4(+) T cell responses against melanoma
in vivo.