1887

Journal of General Virology header logo

Volume 77, Issue 4

Proliferative T cell responses to human papillomavirus type 16 L1 peptides in patients with cervical dysplasia Free

Abstract

Human papillomavirus type 16 (HPV-16) can cause genital warts, cervical dysplasias and carcinoma of the cervix. Cell-mediated immunity is thought to be important in protection against the virus and in its elimination, but little is known about the mechanisms involved. In a cross-sectional study we have demonstrated proliferative T cell responses to peptides representing the HPV-16 L1 capsid protein (aa 199–409) in the peripheral blood of 63% of patients (n = 41) with histological evidence of cervical dysplasia and in 45% of healthy age-matched controls (n = 11). This was achieved by generating short-term T cell lines (STLs) from each individual against a β-galactosidase-HPV-16 L1 (aa 199–409) fusion protein for 2 weeks, and then identifying the HPV epitopes they recognized with overlapping synthetic peptides (15-mers) spanning this region in 3 day specificity assays. Histological grading and HPV typing by PCR were performed on patients’ cervical biopsies taken at the same clinical visit as the peripheral blood samples. An immunogenic region was identified between aa 311–345 in 73% of patients (18% in controls) who responded to HPV-16 L1 (aa 199–409). The number of responders to this region was significantly higher in patients with HPV-16-positive biopsies when compared to those with HPV-16-negative biopsies ( = 0.006), as was the number of responders to individual peptides 311–325 (NLASSNYFPTPSGSM; = 0.04) and 321–335 (PSGSMVTSDAQIFNK; = 0.004) representing this region. The mean level of response to each individual peptide was also higher in the patient group than the controls ( < 0.05). The most significant finding was that all patients with evidence of a current HPV-16 infection responded to one or more L1 peptides ( = 0.0004) and 92% had high grade cervical intraepithelial neoplasia (CIN III). We also found that the CIN III group was more likely to respond to any L1 peptide than either the atypical group ( = 0.04) or the controls ( = 0.05). Data from four individuals showed that the majority of peptide-specific STLs were CD4 but some CD8 STLs were also detected.

  • Received:
  • Accepted:
  • Published Online:
© Journal of General Virology 1996
Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-77-4-593
1996-04-01
2024-04-19
Loading full text...

Full text loading...

/deliver/fulltext/jgv/77/4/JV0770040593.html?itemId=/content/journal/jgv/10.1099/0022-1317-77-4-593&mimeType=html&fmt=ahah

References

  1. Altmann A., Jochmus-Kudielka I., Frank R., Gausepohl H., Moebius U., Gissman L., Meuer S. C. 1992; Definition of immunogenic determinants of the human papillomavirus type 16 nucleoprotein E7. European Journal of Cancer 28:326–333
     [Google Scholar]
  2. Bell J. A., Sundberg J. P., Ghim S.-J., Newsome J., Jenson A. B., Schlegel R. 1994; A formalin-inactivated vaccine protects against mucosal papillomavirus infection: a canine model. Patho-biology 62:194–198
     [Google Scholar]
  3. Comerford S. A., McCance D. J., Dougan G., The J. P. 1991; Identification of T- and B-cell epitopes of the E7 protein of human papillomavirus type 16. Journal of Virology 65:4681–4690
     [Google Scholar]
  4. Davies D. H., Hill C. M., Rothbard J. B., Chain B. M. 1990; Definition of murine T-helper cell determinants in the major capsid protein of human papillomavirus type 16. Journal of General Virology 71:2691–2698
     [Google Scholar]
  5. Doorbar J., Campbell D., Grand R. J., Gallimore P. H. 1986; Identification of the human papillomavirus la E4 gene products. EMBO Journal 5:355–362
     [Google Scholar]
  6. Galloway D. A. 1994; Papillomavirus capsids: a new approach to identify serological markers of HPV infection. Journal of the National Cancer Institute 86:474–475
     [Google Scholar]
  7. Jarrett W. F., Smith K. T., O’Neil B. W., Gaukroger J. M., Chandrachud L. M., Grindlay G. J., McGarvie G. M., Campo M. 1991; Studies on vaccination against papillomaviruses: prophylactic and therapeutic vaccination with recombinant structural proteins. Virology 184:33–42
     [Google Scholar]
  8. Johnson J. C., Burnett A. F., Willet G. D., Young M. A., Doniger J. 1992; High frequency of latent and clinical human papillomavirus cervical infections in immunocompromised human immunodeficiency virus-infected women. Obstetrics and Gynaecology 19:321–327
     [Google Scholar]
  9. Kirnbauer R., Hubbert N. L., Wheeler C. M., Becker T. M., Lowy D. R., Schiller J. T. 1994; A virus-like particle enzyme-linked immunosorbent assay detects serum antibodies in a majority of women infected with human papillomavirus type 16. Journal of the National Cancer Institute 86:494–499
     [Google Scholar]
  10. Koutsky L. A., Galloway D. A., Holmes K. K. 1988; Epidemiology of genital human papillomavirus infection. Epidemiologic Reviews 10:122–163
     [Google Scholar]
  11. Lin Y. L., Borenstein L. A., Selvakumar R., Ahmed R., Wettstein F. O. 1992; Effective vaccination against papilloma development by immunization with L1or L2 structural protein of cottontail rabbit papillomavirus. Virology 187:612–619
     [Google Scholar]
  12. Melbye M., Palefsky J., Gonzales J., Ryder L. P., Nielsen H., Bergmann O., Pindborg J., Biggar R. J. 1990; Immune status as a determinant of human papillomavirus detection and its association with anal epithelial abnormalities. International Journal of Cancer 46:203–206
     [Google Scholar]
  13. Orth G. 1987; Epidermodysplasia verruciformis. In The Papova-viridae pp 199–235 Edited by Salzman N. P., Howley P. M. New York: Plenum Press;
     [Google Scholar]
  14. Ota K., Matsui M., Milford E. L., Mackin G. A., Weiner H. L., Hafler D. A. 1990; T-cell recognition of an immunodominant myelin basic protein epitope in multiple sclerosis. Nature 346:183–187
     [Google Scholar]
  15. Patel D., Shepherd P., Naylor J., McCance D. J. 1989; Reactivities of polyclonal and monoclonal antibodies raised to the major capsid protein of human papillomavirus type 16. Journal of General Virology 70:69–77
     [Google Scholar]
  16. Porrbco R., Penn I., Droegemueller W., Greer B., Makowski E. 1975; Gynaecological malignancies in immunosuppressed organ homograft recipients. Obstetrics and Gynaecology 45:359–364
     [Google Scholar]
  17. Resnick R. M., Cornelissen M. T., Wright D. K., Eichinger G. H., Fox H. S., ter Schegget J., Manos M. M. 1990; Detection and typing of human papillomavirus in archival cervical cancer specimens by DNA amplification with consensus primers. Journal of the National Cancer Institute 82:1477–1484
     [Google Scholar]
  18. Rieber E. P., Rank G. 1994; CDw60: A marker for human CD8+ T helper cells. Journal of Experimental Medicine 119:1385–1390
     [Google Scholar]
  19. Rudlinger R., Smith I. W., Bunney M. H., Hunter J. A. A. 1986; Human papillomavirus infections in a group of renal transplant recipients. British Journal of Dermatology 115:681–692
     [Google Scholar]
  20. Schneider A., Kirchhoff T., Meinhardt G., Gissmann L. 1992; Repeated evaluation of human papillomavirus 16 status in cervical swabs of young women with a history of normal Papanicolaou smears. Obstetrics and Gynaecology 79:683–688
     [Google Scholar]
  21. Sedlacek T. V., Lindheim S., Eder C., Hasty L., Woodland M., Ludomirsky A., Rando R. F. 1989; Mechanism for human papillomavirus transmission at birth. American Journal of Obstetrics and Gynecology 161:55–59
     [Google Scholar]
  22. Shepherd P. S., Tran T. T. T., Rowe A. J., Cridland J. C., Comerford S. A., Chapman M. G., Rayfield L. S. 1992; T-cell responses to the human papillomavirus type 16 E7 protein in mice of different haplotypes. Journal of General Virology 73:1269–1274
     [Google Scholar]
  23. Snijders P. J., van den Brule A., Schrijnemakers H., Snow G., Meijer C., Walboomers A. 1990; The use of general primers in the polymerase chain reaction permits the detection of a broad spectrum of human papillomavirus genotypes. Journal of General Virology 71:173–181
     [Google Scholar]
  24. Stanley K. K., Luzio J. P. 1984; Construction of a new family of high efficiency bacterial expression vectors: identification of cDNA clones coding for human liver proteins. EMBO Journal 3:1429–1434
     [Google Scholar]
  25. Strang G., Hickling J. K., McIndoe G. A. J., Howland K., Wilkinson D., Ikeda H., Rothbard J. B. 1990; Human T-cell responses to human papillomavirus type 16 L1 and E6 synthetic peptides: identification of T-cell determinants, HLA-DR restriction and virus type specificity. Journal of General Virology 71:423–431
     [Google Scholar]
  26. Tagami H., Oguchi M., Ofuji S. 1983; Immunological aspects of wart regression with special reference to regression phenomenon of numerous flat warts. An experiment on tumour immunity in man by nature. Journal of Dermatology 10:1–12
     [Google Scholar]
  27. Tindle R. W., Fernando G. J. P., Sterling J. C., Frazer I. H. 1991; A public T-helper cell epitope of the E7 transforming protein of human papillomavirus type 16 provides cognate help for several E7 B-cell epitopes from cervical cancer associated human papillomavirus genotypes. Proceedings of the National Academy of Sciences, USA 88:5887–5891
     [Google Scholar]
  28. van den Brule A. J., Snijders P. J., Raaphorst P. M., Schrijnemakers H. F., Delius H., Gissmann L., Meijer C. J., Walboomers J. M. 1992; General primer polymerase chain reaction in combination with sequence analysis for identification of potentially novel human papillomavirus genotypes in cervical lesions. Journal of Clinical Microbiology 30:1716
     [Google Scholar]
  29. Weiner H. L., Mackin G. A., Matsui M., Orav E. J., Khoury D. M., Dawson S. J., Hafler D. A. 1993; Double-blind pilot trial of oral tolerization with myelin antigens in multiple sclerosis. Science 259:1321–1324
     [Google Scholar]
  30. Wright D., Manos M. 1990; Sample preparation from paraffin-embedded tissues. In PCR Protocols: A Guide to Methods and Applications pp 153–158 Edited by Innis M. A., Gelfand D. H., Sninsky J. J., White T. J. San Diego: Academic Press;
     [Google Scholar]
  31. Zur Hausen H. 1991; Human papillomavirus in the pathogenesis of anogenital cancer. Virology 184:9–13
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-77-4-593
Loading
Proliferative T cell responses to human papillomavirus type 16 L1 peptides in patients with cervical dysplasia
J. Gen. Virol. 77, 593 (1996); https://doi.org/10.1099/0022-1317-77-4-593
/content/journal/jgv/10.1099/0022-1317-77-4-593
/content/journal/jgv/10.1099/0022-1317-77-4-593
Loading

Data & Media loading...

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error