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TUMOR-ASSOCIATED E6 PROTEIN OF HUMAN PAPILLOMAVIRUS TYPE-16 CONTAINS AN UNUSUAL H-2K(B)-RESTRICTED CYTOTOXIC T-CELL EPITOPE

GAO, LQ; WALTER, J; TRAVERS, P; STAUSS, H; CHAIN, BM; (1995) TUMOR-ASSOCIATED E6 PROTEIN OF HUMAN PAPILLOMAVIRUS TYPE-16 CONTAINS AN UNUSUAL H-2K(B)-RESTRICTED CYTOTOXIC T-CELL EPITOPE. J IMMUNOL , 155 (12) 5519 - 5526.

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Abstract

We previously showed that CTL from H-2(b) mice immunized against the E6 protein of human papilloma virus (HPV) type 16 recognized a 10-mer peptide corresponding to amino acids 131 to 140. We show in this study that the minimal epitope, 130 to 137, is a 8-mer peptide presented by H-2K(b) class I molecules. At position P8, the 130 to 137 peptide contains a hydrophobic methionine anchor residue, but P3 and P5 do not contain the typical anchor residues that are frequently found in K-b-bound peptides, Analysis with alanine-substituted peptides indicates that the tryptophan at P3 acts as an alternative anchor mediating K-b binding, while an arginine at P2 is a TCR contact residue. Synthetic 9-mer peptides corresponding to residues 130 to 138 are as efficiently recognized by CTL as 130 to 137 peptides. Analysis of extracts of EG-expressing cells suggests that Ag processing may produce multiple peptides containing the minimal 130 to 137 epitope, In vitro binding studies indicate that K-b binding of peptide 130 to 137 is approximately five orders of magnitude less efficient than K-b binding of previously identified CTL epitopes. In contrast, the E6 protein contains another potential CTL epitope in the region of amino acids 41 to 50, A synthetic peptide spanning this region binds very strongly to Kb and is capable of stimulating a strong peptide-specific CTL response. In the context of the whole protein, however, this epitope remains cryptic.

Type: Article
Title: TUMOR-ASSOCIATED E6 PROTEIN OF HUMAN PAPILLOMAVIRUS TYPE-16 CONTAINS AN UNUSUAL H-2K(B)-RESTRICTED CYTOTOXIC T-CELL EPITOPE
Keywords: CLASS-I MOLECULES, LYMPHOCYTES-T, DEPENDS, PEPTIDE, VIRUS, MOTIF
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Computer Science
URI: http://discovery.ucl.ac.uk/id/eprint/103360
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