Naturally processed and HLA-B8-presented HPV16 E7 epitope recognized by T cells from patients with cervical cancer.
Several major histocompatibility complex (MHC) alleles have been reported to present peptides derived from the HPV16 E7 oncoprotein to T cells. We describe an overrepresentation of the HLA-B8 allele (28.44%) in cervical cancer patients as compared to the MHC class I allele frequency in a local healthy control population (18.80%) and the identification of an HLA-B8-binding peptide TLHEYMLDL (HPV16 E7(7-15)), which is able to drive HPV16 E7-specific and MHC class I-restricted T-cell responses in peripheral blood lymphocytes from healthy individuals. TLHEYMLDL-specific T cells recognize the naturally processed and presented peptide on HPV16+ cervical cancer cells transfected with the HLA-B8 gene defined by IFN-gamma production. This peptide epitope is also recognized by freshly harvested tumor-infiltrating T cells or T cells from tumor-draining lymph nodes from patients with cervical cancer determined by flow cytometry as well as by tetramer in situ staining. HLA-B8-restricted HPV E7(7-15)-specific T cells reside predominantly in the CD8+ CD45RA+ CCR7+ precursor or in the differentiated CD8+ CD45RA+ CCR7- T-cell population.
Oerke
Sebastian
S
Department of Medical Microbiology, University of Mainz, Mainz, Germany.
Höhn
Hanni
H
Zehbe
Ingeborg
I
Pilch
Henryk
H
Schicketanz
Karl-Heinz
KH
Hitzler
Walter E
WE
Neukirch
Claudia
C
Freitag
Kirsten
K
Maeurer
Markus J
MJ
D000483:Alleles; D017951:Antigen Presentation; D016827:CD8 Antigens / Q000096:biosynthesis; D000939:Epitopes / Q000737:chemistry; D005260:Female; D005434:Flow Cytometry; D005805:Genes, MHC Class I; D015795:HLA-B8 Antigen / Q000378:metabolism*; D006801:Humans; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D008198:Lymph Nodes / Q000378:metabolism; D008207:Lymphatic Metastasis; D008214:Lymphocytes / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D050725:Papillomavirus E7 Proteins; D010455:Peptides / Q000737:chemistry; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000378:metabolism
C515370:CCR7 protein, human; D016827:CD8 Antigens; D000939:Epitopes; D015795:HLA-B8 Antigen; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D010455:Peptides; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; C059731:oncogene protein E7, Human papillomavirus type 16; D017493:Leukocyte Common Antigens