Epitopes and reactivity in other viral diseases

[Ganseerpel]

Interspecies crossreactivity HPV/Coronavirus?

Journal of Virology, May 2003, p. 5464-5474, Vol. 77, No. 9
0022-538X/03/$08.00+0 DOI: 10.1128/JVI.77.9.5464-5474.2003

Human Papillomavirus Type 16 E7 Peptide-Directed CD8+ T Cells from Patients with Cervical Cancer Are Cross-Reactive with the Coronavirus NS2 Protein
Katja Nilges,1 Hanni H?hn,1 Henryk Pilch,2 Claudia Neukirch,1 Kirsten Freitag,1 P. J. Talbot,3 and Markus J. Maeurer1*
Department of Medical Microbiology, University of Mainz,1 Department of Gynecology and Obstetrics, Johannes Gutenberg University, Mainz, Germany,2 Human Health Research Center, INRS-Institut Armand Frappier, University of Quebec, Laval, Canada3

Received 9 August 2002/ Accepted 28 January 2003

Human papillomavirus type 16 (HPV16) E6 and E7 oncoproteins are required for cellular transformation and represent candidate targets for HPV-specific and major histocompatibility complex class I-restricted CD8+-T-cell responses in patients with cervical cancer. Recent evidence suggests that cross-reactivity represents the inherent nature of the T-cell repertoire. We identified HLA-A2 binding HPV16 E7 variant peptides from human, bacterial, or viral origin which are able to drive CD8+-T-cell responses directed against wild-type HPV16 E7 amino acid 11 to 19/20 (E711-19/20) epitope YMLDLQPET(T) in vitro. CD8+ T cells reacting to the HLA-A2-presented peptide from HPV16 E711-19(20) recognized also the HLA-A2 binding peptide TMLDIQPED (amino acids 52 to 60) from the human coronavirus OC43 NS2 gene product. Establishment of coronavirus NS2-specific, HLA-A2-restricted CD8+-T-cell clones and ex vivo analysis of HPV16 E7 specific T cells obtained by HLA-A2 tetramer-guided sorting from PBL or tumor-infiltrating lymphocytes obtained from patients with cervical cancer showed that cross-reactivity with HPV16 E711-19(20) and coronavirus NS252-60 represents a common feature of this antiviral immune response defined by cytokine production. Zero of 10 patients with carcinoma in situ neoplasia and 3 of 18 patients with cervical cancer showed 0.1% HPV16 E7-reactive T cells in CD8+ peripheral blood lymphocytes. In vivo priming with HPV16 was confirmed in patients with cervical cancer or preinvasive HPV16-positive lesions using HLA-A2 tetramer complexes loaded with the E6-derived epitope KLPQLCTEL. In contrast, we could not detect E6-reactive T cells in healthy individuals. These data imply that the measurement of the HPV16 E711-19(20) CD8+-T-cell response may reflect cross-reactivity with a common pathogen and that variant peptides may be employed to drive an effective cellular immune response against HPV.

f-t: http://jvi.asm.org/cgi/content/abstract/jvi;77/9/5464

 

[AlaskaDenise]

Re: Epitopes and reactivity in other viral diseases

In ordinary language, is this saying that we could possibly treat HPV with a coronavirus?

.

 

[Ganseerpel]

Re: Epitopes and reactivity in other viral diseases

Hi Denise,

When it occurs before, yes, but we would call it sort of prophylaxis, not really treatment. This is interesting, because it demonstrates that one and the same starting point (infection with agens A) can entail a different natural history depending on what happened before i.e. how the individual whas been primed. We have seen that in a similar process birds "primed" with LPAI infection are better off when infected with HPAI viruses.