In conclusion, the difference in therapeutic effect between LGG wild-type and dltD mutant in vivo suggests a role for the cell surface of the wild-type LGG strain in determining its therapeutic efficacy. Interestingly, these results with the

LGG dltD mutant show the potential of modifying the cell surface of probiotic strains for better treatment of IBD with probiotics. Combining these modified probiotic strains with the concept of ‘designer probiotics’[62] seems to be appealing for the future. One example of such a ‘designed’ strain is the IL-10-secreting Lactococcus lactis strain that shows potential in treatment of IBD [63,64]. Further in vitro studies are required to reveal the molecular mechanisms underlying the beneficial effects of this altered cell surface.

I.C. holds a PhD grant of the Kinase Inhibitor Library clinical trial Institute for the Promotion of Innovation through Science and Technology in Flanders (IWT–Vlaanderen). D.B. holds a senior researcher grant of FWO–Vlaanderen. Additionally, this work was supported partially by the FWO–Vlaanderen through project G.0236·07. We thank K. Geboes for helpful KPT-330 mouse discussions regarding the set-up of the animal experiments. The authors also gratefully acknowledge L. Ophalvens for excellent technical assistance. We thank the anonymous reviewers for their helpful comments and suggestions. The authors declare no conflicts of interest. “
“The Melan-A/MART-126-35 antigenic peptide is one of the best studied human tumor-associated antigens. It is expressed in healthy melanocytes and malignant melanoma and is recognized by CD8+ T cells in the context of the MHC class I molecule HLA-A*0201. While an unusually large repertoire of CD8+ T cells specific for this antigen has been documented, the reasons for its generation have remained

elusive. In this issue of the European Journal of Immunology, Pinto et al. [Eur. J. Immunol. 2014. 44: 2811–2821] uncover one important mechanism Farnesyltransferase by comparing the thymic expression of the Melan-A gene to that in the melanocyte lineage. This study shows that medullary thymic epithelial cells (mTECs) dominantly express a truncated Melan-A transcript, the product of misinitiation of transcription. Consequently, the protein product in mTECs lacks the immunodominant epitope spanning residues 26–35, thus precluding central tolerance to this antigen. In contrast, melanocytes and melanoma tumor cells express almost exclusively the full-length Melan-A transcript, thus providing the target antigen for efficient recognition by HLA-A2-restricted CD8+ T cells. The frequency of these alternative gene transcription modes may be more common than previously appreciated and may represent an important factor modulating the efficiency of central tolerance induction in the thymus.