Peptide HER2(776-788) represents a naturally processed broad MHC class II-restricted T cell epitope.
HER2/neu-derived peptides inducing MHC class II-restricted CD4+ T helper lymphocyte (Th) responses, although critical for tumour rejection, are not thoroughly characterized. Here, we report the generation and characterization of CD4+ T cell clones specifically recognizing a HER-2/neu-derived peptide (776-788) [designated HER2(776-788)]. Such clones yielded specific proliferative and cytokine [gamma-interferon(IFN)-gamma] responses when challenged with autologous dendritic cells (DCs) loaded with HER2(776-788). By performing blocking studies with monoclonal antibodies (MAbs) and by using DCs from allogeneic donors sharing certain HLA-DR alleles, we found that HER2(776-788) is a promiscuous peptide presented, at least, by DRB5*0101, DRB1*0701 and DRB1*0405 alleles. One TCRV beta 6.7+ clone recognized the HLA-DRB5*0101+ FM3 melanoma cell line transfected with a full length HER-2/neu cDNA. Moreover, this clone recognized the HER-2/neu+ SKBR3 breast cancer cell line induced to express HLA-DR, thus demonstrating that HER2(776-788) represents a naturally processed and presented epitope. Our data demonstrate that helper peptide HER2(776-788) represents a promiscuous epitope binding to at least three HLA-DR alleles, thus offering a broad population coverage. The use of antigenic peptides presented by major histocompatibility complex (MHC) class II in addition to those presented by class I may improve the therapeutic efficacy of active immunization.
Sotiriadou
R
R
Cancer Immunology Immunotherapy Center, Saint Savas Cancer Hospital, Athens 11522, Greece.
Perez
S A
SA
Gritzapis
A D
AD
Sotiropoulou
P A
PA
Echner
H
H
Heinzel
S
S
Mamalaki
A
A
Pawelec
G
G
Voelter
W
W
Baxevanis
C N
CN
Papamichail
M
M
D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000276:immunology*; D002460:Cell Line; D002478:Cells, Cultured; D002999:Clone Cells; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006684:HLA-DR Antigens / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D009369:Neoplasms / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology*; D010455:Peptides / Q000276:immunology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D018984:Epitopes, T-Lymphocyte; D006684:HLA-DR Antigens; D007371:Interferon-gamma; D010446:Peptide Fragments; D010455:Peptides; D018719:Erb-b2 Receptor Tyrosine Kinases; C446482:HER2(776-788)