5.3
TITLE: MOLECULAR MODELING STUDIES OF A PEPTIDE FROM HUMAN PAILLOMA VIRUS TYPE 16 E7 PROTEIN WITH MOTIF FOR HLA-DQ6 (B*0602) SHOWS GOOD BINDING PROPERTIES

Carani B Sanjeevi ¹, Terry P Lybrand ², Stefan Stevanovic ³ and Hans-Goerg Rammensee ³.

¹Dept of Molecular Medicine, Karolinska Institute, Stockholm, Sweden; ²Dept of Structural Biologu, Vanderbildt University, Nashville, TN and ³Dept of Immunology, University of Tubingen, Tubingen, Germany.

Carcinoma cervix is associated with Human Papilloma virus (HPV). DQ6 (DQB1*0602) has been shown to be positively associated with Cervical Intraepithelial Neoplasia (CIN), HPV16 positive CIN and cervical cancer in Swedish women from Northern Sweden. The aim of the study was to identify peptide sequence by screening E7 protein using motifs from DQ6 molecule, identified by peptide elution from DQ6 and peptide sequencing. Several peptides were identified. The most promising one had the sequence QAE-PDRAHYNIV-TFC with homology to position 44 to 58 of E7 protein. Molecular modeling studies were done in silicon graphics workstation using the software 'PSSHOW' to construc the peptides. We had earlier modeled the DQ6 molecule by homology modeling using the co-ordinates of the DQ8 crystal structure kindly provided by late Don Wiley. The docking studies using the peptide QAE-PDRAHYNIV-TFC suggested the binding motif to be P at position 4 fitting into P1 pocket, A at position 7 into P4 pocket, Y at position 9 at P6 pocket and V at position 12 fitting neatly into P9 pocket. An alternate model was also constructed where, R at position 6 fitting into P1 pocket, Y at position 9 fitting into P4 pocket, I at position 11 fitting into P6 pocket and F at position 14 fitting into P9 pocket. This model also bound very well into DQ6 groove but the fit was better with the earlier model. These data suggest that the HPV-16 peptide binding to DQ6 associated with CIN and Cervical Cancer could be a good candidate for T cell studies. These studies involve estimation of precursor T cells in women with HPV 16 infection who have cleared the infection compared to those who have not cleared the infection at one-year follow-up. These T cell studies are underway that would help us with planning prediction strategies.