title: Human papilloma virus specific T cells infiltrating cervical cancer and draining lymph nodes show remarkably frequent use of HLA-DQ and -DP as a restriction element.
abstract: Human papillomavirus (HPV)-induced malignancies are frequently infiltrated by lymphocytes. To comprehend the contribution of HPV-specific T cells in this anti-tumor response we developed a method that allowed the analysis of the presence and specificity of cervix-infiltrating and draining lymph node resident T cells in a group of 74 patients with cervical malignancies, 54 of which were induced by HPV16 or HPV18. We detected the presence of HPV16 or HPV18-specific T cells in at least 23 of the 54 HPV-16 or -18 positive patients, and not in the 20 controls. Detailed studies resulted in the identification of 17 novel CD4+ and CD8+ T cell epitopes and their HLA-restriction elements, and also revealed that the HPV-specific immune response was aimed at both E6 and E7 and showed no preferential recognition of immunodominant regions. Unexpectedly, the vast majority of the CD4+ T cell epitopes were presented in the context of the less abundantly expressed HLA-DQ and HLA-DP molecules. Since the identified T cell epitopes constitute physiological targets in the immune response to HPV16 and HPV18 positive tumors they will be valuable for detailed studies on the interactions between the tumor and the immune system. This is crucial for the optimization of cancer immunotherapy in patients with pre-existing tumor-immunity.
authors.affiliation: Department of Clinical Oncology, Leiden University Medical Center, 2333 ZA, Leiden, The Netherlands.
authors.forename: Sytse J
authors.initials: SJ
authors.lastname: Piersma
authors.forename: Marij J P
authors.initials: MJ
authors.lastname: Welters
authors.forename: Jeanette M
authors.initials: JM
authors.lastname: van der Hulst
authors.forename: Judith N
authors.initials: JN
authors.lastname: Kloth
authors.forename: Kitty M C
authors.initials: KM
authors.lastname: Kwappenberg
authors.forename: Baptist J
authors.initials: BJ
authors.lastname: Trimbos
authors.forename: Cornelis J M
authors.initials: CJ
authors.lastname: Melief
authors.forename: Bart W
authors.initials: BW
authors.lastname: Hellebrekers
authors.forename: Gert Jan
authors.initials: GJ
authors.lastname: Fleuren
authors.forename: Gemma G
authors.initials: GG
authors.lastname: Kenter
authors.forename: Rienk
authors.initials: R
authors.lastname: Offringa
authors.forename: Sjoerd H
authors.initials: SH
authors.lastname: van der Burg
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D002478:Cells, Cultured; D000939:Epitopes / Q000276:immunology; D005260:Female; D006682:HLA-DP Antigens / Q000276:immunology / Q000378:metabolism*; D006683:HLA-DQ Antigens / Q000276:immunology / Q000378:metabolism*; D052162:Human papillomavirus 16 / Q000276:immunology*; D052161:Human papillomavirus 18 / Q000276:immunology*; D006801:Humans; D008198:Lymph Nodes / Q000276:immunology* / Q000473:pathology / Q000821:virology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000276:immunology / Q000473:pathology / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000473:pathology / Q000821:virology
chemical_list: D000939:Epitopes; D006682:HLA-DP Antigens; D006683:HLA-DQ Antigens