RT Journal Article
SR Electronic
T1 Codon arrangement modulates MHC-I peptides presentation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.06.03.078824
DO 10.1101/2020.06.03.078824
A1 Tariq Daouda
A1 Maude Dumont-Lagacé
A1 Albert Feghaly
A1 Yahya Benslimane
A1 Rébecca Panes
A1 Mathieu Courcelles
A1 Mohamed Benhammadi
A1 Lea Harrington
A1 Pierre Thibault
A1 François Major
A1 Yoshua Bengio
A1 Étienne Gagnon
A1 Sébastien Lemieux
A1 Claude Perreault
YR 2020
UL http://biorxiv.org/content/early/2020/06/04/2020.06.03.078824.abstract
AB MHC-I associated peptides (MAPs) play a central role in the elimination of virus-infected and neoplastic cells by CD8 T cells. However, accurately predicting the MAP repertoire remains difficult, because only a fraction of the transcriptome generates MAPs. In this study, we investigated whether codon arrangement (usage and placement) regulates MAP biogenesis. We developed an artificial neural network called Codon Arrangement MAP Predictor (CAMAP), predicting MAP presentation solely from mRNA sequences flanking the MAP coding regions, while excluding the MAP-coding codons per se. CAMAP predictions were significantly more accurate when using codon sequences than amino acid sequences. Furthermore, predictions were independent of mRNA expression and MAP binding affinity to MHC-I molecules, and applied to several cell types and species. Combining MAP binding affinity, transcript expression level and CAMAP scores was particularly useful to ameliorate predictions of MAP derived from lowly expressed transcripts. Using an in vitro assay, we showed that varying the synonymous codons in the regions flanking MAP sequences (without changing the amino acid sequence) resulted in significant modulation of MAP presentation at the cell surface. Taken together, our results demonstrate the role of codon arrangement in the regulation of MAP presentation and support integration of both translational and post-translational events in predictive algorithms to ameliorate modeling of the immunopeptidome.Competing Interest StatementThe authors have declared no competing interest.