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 Daouda, Tariq
A1 Dumont-Lagacé, Maude
A1 Feghaly, Albert
A1 Benslimane, Yahya
A1 Panes, Rébecca
A1 Courcelles, Mathieu
A1 Benhammadi, Mohamed
A1 Harrington, Lea
A1 Thibault, Pierre
A1 Major, François
A1 Bengio, Yoshua
A1 Gagnon, Étienne
A1 Lemieux, Sébastien
A1 Perreault, Claude
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.