4/ Also, Müller et al.(PMID:29104575) proposed that if the WT peptide is presented, the mutated version is more likely to be presented. We searched for WT counterpart peptides in an in-house dataset of 1000s of immunopept. samples and found a higher proportion of presented peptides in responders.

3/ However, HLA-I binding affinity doesn’t guarantee real peptide presentation. I explored PDAC neoantigen presentation using two approaches.
First, Cysteines are generally depleted in the immunopeptidome. Notably, non-responder peptides had a 3-fold increase in cysteine-containing peptides.

2/ Responder peptides had a higher HLA-I affinity than those in non-responders (as expected). ~50% of the non-immunogenic peptides weren’t binders (by NetMHC). This suggests that one distinction between responders and non-responders lies in the quality of the neoantigens included in the vaccine.

I am very happy to share that last week, I had the opportunity to present my research at the Winter Meeting of the Catalan Society of Immunology. But I feel even more honored to have presented in a session chaired by my first mentor in immunology, Dolores Jaraquemada.

6/ Structural predictions revealed that TE-derived exons preferentially fold into alpha helices, thanks to their distinct amino acid composition. These exons can boost the alpha-helix content of host proteins, a structural feature that increases during protein evolution.

5/ JET-ORFs have defined subcellular locations, which can be different compared to the canonical isoform. Their functions can also differ. Through JET-KOs and splicing modulation, we observed that these functions are biologically relevant at endogenous levels.

4/ Some JETs show evolutionary conservation, particularly those highly recurrent across samples. Conserved JETs are more frequently used among all splicing isoforms of a gene, and this usage increases across evolution. Thanks to @lquintanamurci.bsky.social and Maxime Rotival for the job!

3/ Overall, JETs have been acquired recently during evolution. However, they tend to appear in older, more ancient genes, creating an interesting dichotomy: recent TE-derived exons preferentially integrated into ancient genes.

2/ Using RiboSeq and proteomics, we identified a population of translated isoforms containing exonized TEs (JET-ORFs). We propose that these TE-containing isoforms are not “only” merely transcriptional noise but a snapshot of evolving proteins under natural selection.