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A consensus epitope prediction approach identifies the breadth of murine TCD8+-cell responses to vaccinia virus

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Abstract

The value of predictive algorithms for identifying CD8+ T (TCD8+)-cell epitopes has not been adequately tested experimentally. Here we demonstrate that conventional bioinformatic methods predict the vast majority of TCD8+-cell epitopes derived from vaccinia virus WR strain (VACV-WR) in the H-2b mouse model. This approach reveals the breadth of T-cell responses to vaccinia, a widely studied murine viral infection model, and may provide a tool for developing comprehensive antigenic maps of any complex pathogen.

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Figure 1: Identification of H-2b–restricted epitopes derived from VACV-WR–infected C57BL/6 mice.
Figure 2: The identified epitopes account for the majority of the TCD8+-cell response to VACV-WR.

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Acknowledgements

This study was funded by the National Institutes of Health (contract no. HHSN266200400024C, and RO1 grant no. RO1-AI-56268. D.C.T. is the recipient of an National Health and Medical Research Council (Australia) Howard Florey Centenary Fellowship no. 224273.

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Authors and Affiliations

  1. La Jolla Institute for Allergy and Immunology, 3030 Bunker Hill Street, Suite 326, San Diego, 92109, California, USA

    Magdalini Moutaftsi, Bjoern Peters, Valerie Pasquetto, John Sidney, Huynh-Hoa Bui, Howard Grey & Alessandro Sette

  2. Division of Immunology and Infectious Diseases, Queensland Institute of Medical Research, Herston, Australia

    David C Tscharke

Authors
  1. Magdalini Moutaftsi
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  2. Bjoern Peters
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  3. Valerie Pasquetto
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  4. David C Tscharke
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  5. John Sidney
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  6. Huynh-Hoa Bui
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  7. Howard Grey
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  8. Alessandro Sette
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Correspondence to Alessandro Sette.

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Supplementary information

Supplementary Fig. 1

Using scoring matrices to predict the affinity of peptides to MHC-I molecules. (PDF 23 kb)

Supplementary Fig. 2

Analyzing prediction performance post-hoc. (PDF 73 kb)

Supplementary Table 1

Summary of epitope characteristics. (PDF 52 kb)

Supplementary Table 2

Structural characteristics of antigens recognized. (PDF 45 kb)

Supplementary Table 3

Summary of structural characteristics of VACV-WR antigens recognized by C57BL/6. mice (PDF 37 kb)

Supplementary Data 1

Scoring matrices used for the individual predictions. (PDF 323 kb)

Supplementary Data 2

Peptides from Vaccinia WR predicted to bind MHC molecules. (PDF 317 kb)

Supplementary Methods (PDF 99 kb)

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Moutaftsi, M., Peters, B., Pasquetto, V. et al. A consensus epitope prediction approach identifies the breadth of murine TCD8+-cell responses to vaccinia virus. Nat Biotechnol 24, 817–819 (2006). https://doi.org/10.1038/nbt1215

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  • DOI: https://doi.org/10.1038/nbt1215

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