TY - JOUR
T1 - Identification of MAGE-3 epitopes presented by HLA-DR molecules to CD4+ T lymphocytes
AU - Chaux, Pascal
AU - Vantomme, Valérie
AU - Stroobant, Vincent
AU - Thielemans, Kris
AU - Corthals, Jurgen
AU - Luiten, Rosalie
AU - Eggermont, Alexander M.M.
AU - Boon, Thierry
AU - Van Der Bruggen, Pierre
PY - 1999/3/1
Y1 - 1999/3/1
N2 - MAGE-type genes are expressed by many tumors of different histological types and not by normal cells, except for male germline cells, which do not express major histocompatibility complex (MHC) molecules. Therefore, the antigens encoded by MAGE-type genes are strictly tumor specific and common to many tumors. We describe here the identification of the first MAGE-encoded epitopes presented by histocompatibility leukocyte antigen (HLA) class II molecules to CD4+ T lymphocytes. Monocyte-derived dendritic cells were loaded with a MAGE-3 recombinant protein and used to stimulate autologous CD4+ T cells. We isolated CD4+ T cell clones that recognized two different MAGE-3 epitopes, MAGE-3(114-127) and MAGE-3(121-134), both presented by the HLA-DR13 molecule, which is expressed in 20% of Caucasians. The second epitope is also encoded by MAGE-1, -2, and -6. Our procedure should be applicable to other proteins for the identification of new tumor-specific antigens presented by HLA class II molecules. The knowledge of such antigens will be useful for evaluation of the immune response of cancer patients immunized with proteins or with recombinant viruses carrying entire genes coding for tumor antigens. The use of antigenic peptides presented by class II in addition to peptides presented by class I may also improve the efficacy of therapeutic antitumor vaccination.
AB - MAGE-type genes are expressed by many tumors of different histological types and not by normal cells, except for male germline cells, which do not express major histocompatibility complex (MHC) molecules. Therefore, the antigens encoded by MAGE-type genes are strictly tumor specific and common to many tumors. We describe here the identification of the first MAGE-encoded epitopes presented by histocompatibility leukocyte antigen (HLA) class II molecules to CD4+ T lymphocytes. Monocyte-derived dendritic cells were loaded with a MAGE-3 recombinant protein and used to stimulate autologous CD4+ T cells. We isolated CD4+ T cell clones that recognized two different MAGE-3 epitopes, MAGE-3(114-127) and MAGE-3(121-134), both presented by the HLA-DR13 molecule, which is expressed in 20% of Caucasians. The second epitope is also encoded by MAGE-1, -2, and -6. Our procedure should be applicable to other proteins for the identification of new tumor-specific antigens presented by HLA class II molecules. The knowledge of such antigens will be useful for evaluation of the immune response of cancer patients immunized with proteins or with recombinant viruses carrying entire genes coding for tumor antigens. The use of antigenic peptides presented by class II in addition to peptides presented by class I may also improve the efficacy of therapeutic antitumor vaccination.
KW - Histocompatibility leukocyte antigen class II
KW - Human
KW - Invariant chain
KW - Peptide
KW - Tumor
UR - http://www.scopus.com/inward/record.url?scp=0033103512&partnerID=8YFLogxK
U2 - 10.1084/jem.189.5.767
DO - 10.1084/jem.189.5.767
M3 - Article
C2 - 10049940
AN - SCOPUS:0033103512
SN - 0022-1007
VL - 189
SP - 767
EP - 777
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 5
ER -