Viral infection causes a shift in the self peptide repertoire presented by human MHC class I molecules

Spencer, Charles T., Bezbradica, Jelena S., Ramos, Mireya G., Arico, Chenoa D., Conant, Stephanie B., Gilchuk, Pavlo, Gray, Jennifer J., Zheng, Mu, Niu, Xinnan, Hildebrand, William, Link, Andrew J. and Joyce, Sebastian (2015) Viral infection causes a shift in the self peptide repertoire presented by human MHC class I molecules. Proteomics - Clinical Applications, 9 11-12: 1035-1052. doi:10.1002/prca.201500106

Author Spencer, Charles T.
Bezbradica, Jelena S.
Ramos, Mireya G.
Arico, Chenoa D.
Conant, Stephanie B.
Gilchuk, Pavlo
Gray, Jennifer J.
Zheng, Mu
Niu, Xinnan
Hildebrand, William
Link, Andrew J.
Joyce, Sebastian
Title Viral infection causes a shift in the self peptide repertoire presented by human MHC class I molecules
Journal name Proteomics - Clinical Applications   Check publisher's open access policy
ISSN 1862-8354
Publication date 2015-12-01
Sub-type Article (original research)
DOI 10.1002/prca.201500106
Open Access Status Not Open Access
Volume 9
Issue 11-12
Start page 1035
End page 1052
Total pages 18
Place of publication Weinheim, Germany
Publisher Wiley-VCH Verlag
Language eng
Formatted abstract
Purpose:  MHC class I presentation of peptides allows T cells to survey the cytoplasmic protein milieu of host cells. During infection, presentation of self peptides is, in part, replaced by presentation of microbial peptides. However, little is known about the self peptides presented during infection, despite the fact that microbial infections alter host cell gene expression patterns and protein metabolism.

Experimental design:  The self peptide repertoire presented by HLA-A*01;01, HLA-A*02;01, HLA-B*07;02, HLA-B*35;01, and HLA-B*45;01 (where HLA is human leukocyte antigen) was determined by tandem MS before and after vaccinia virus infection.

Results:  We observed a profound alteration in the self peptide repertoire with hundreds of self peptides uniquely presented after infection for which we have coined the term “self peptidome shift.” The fraction of novel self peptides presented following infection varied for different HLA class I molecules. A large part (approximately 40%) of the self peptidome shift arose from peptides derived from type I interferon-inducible genes, consistent with cellular responses to viral infection. Interestingly, approximately 12% of self peptides presented after infection showed allelic variation when searched against approximately 300 human genomes.

Conclusion and clinical relevance:  Self peptidome shift in a clinical transplant setting could result in alloreactivity by presenting new self peptides in the context of infection-induced inflammation.
Keyword Infection
Minor histocompatibility
Self peptides
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
Institute for Molecular Bioscience - Publications
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