The 2nd CAPSTONE networkwide virtual meeting took place between the 15th and 17th of March, having the form of scientific training sessions that were delivered as inspiring lectures from our platform’s acknowledged supervisors. The main emphasis was given on ERAPs in antigen processing and presentation, structural insights for the ERAPs/IRAP enzymes, and their genetic implications.

Programme

Programme Day 1 – 15th March 2022

Time

Scientific Workshop - Part1

Presenter

3pm-4pm

Antigen processing and presentation to T cells, with emphasis on the role of trimming by the ERAPs

Pr P. van ENDERT, University of Paris, FR

 

ESR presentation

Presenter

4pm-5pm

Effects of Modulation of ERAP1 activity in antigen processing and presentation

Shami ALVAREZ MOURID, University of Southampton, UK

 

Programme Day 2 – 16th March 2022

Time

Scientific workshop - Part2

Presenter

3pm-4pm

Structures of ERAPs

Dr E. STRATIKOS, NCSR Demokritos & University of Athens, GR

 

ESR presentation

Presenter

4pm-5pm

Development of Drug Delivery Systems for ERAP/IRAP Modulators

Filippa VASCONCELOS, Inocure, CZ

 

Programme Day 3 – 17th March 2022

Time

Scientific workshop - Part3

Presenter

3pm-4pm

"Basics" around the genetics of ERAP1, ERAP2, LNPEP

Dr J. KUIPER, UMCU, Utrecht, NL

 

ESR presentation

Presenter

4pm-5pm

Transcriptional profiling of ERAPs in human blood dendritic cells in different immune related diseases

Filippa VASCONCELOS, Inocure, CZ

 

Design, synthesis and evaluation of phosphinic transition-state analogues of ERAP/IRAP: description of the project and first results

Sandra LLAMAS RIZO, University of Athens, GR

Scientific workshop

  

 

 

 

 

  • Expert immunologist Pr. Peter van Endert (University Paris Descartes, FR) gave a stimulating speech centered around antigen processing and presentation, starting with basic principles of innate and adaptive immunity. The focus was moved to the peptide trimming role of ERAP1/2 and the related biochemical downstream pathway leading to the optimal presentation of antigenic peptides onto the MHC-I molecules that play a crucial role in eliciting a potent T-cytotoxic immune response. Key elements for ERAP1/2 (molecular identity, expression pattern, cellular localization, mechanism of action, substrate specificity, up-and downregulation) were disseminated.

 

 

 

  

  • On the second day of the meeting, the scientific workshop was provided by Dr. Efstratios Stratikos (NCSR Demokritos & National and Kapodistrian University of Athens, GR). Dr. Stratikos gave a very informative and interesting talk on the structures of ERAPs. Starting from the importance of knowing the structure of proteins, to the methods used for structure determination and visualization, he focused on presenting the structures and the conformational changes of ERAP1/2, and IRAP. During the workshop, it was shown that ERAP1/2 have similar overall structures but have differences in specificity pockets. Generally, all aminopeptidases have large internal cavities, conserved active sites, distinct specificity pockets, and undergo large conformational changes when a peptide is bound in the catalytic site. Dr. Stratikos highlighted that rational drug design is very difficult and conformational dynamics are the key to their function.
 
 
 

 

  • On the third day, specialized researcher Dr. Jonas Kuiper (University Medical Center Utrecht, NL) presented up-to-date information regarding ERAPs and their genetic variations. Human predisposition on different autoimmune diseases (AS, BD, BU, psoriasis) has been linked with genetic polymorphisms on ERAPs that influence their expression levels and enzymatic activities. ERAP1 displays more than 10 single nucleotide polymorphisms (SNPs) resulting in human allotypes with varying frequencies of appearance. ERAP2 exhibits 2 major common haplotypes (HapA, HapB) regulating the prevalence of autoimmunity risk. Dr. Kuiper pointed out that is not only the presence of ERAP the problem in some conditions, but its high expression, so enzymatic activity, and expression are both important in the biology of ERAPs.

 

ESR presentations

 

  • ESR5 Shami Álvarez Mourid (Centre for Cancer Immunology, University of Southampton, UK) shared some interesting early results about his project titled “Effects of Modulation of ERAP1 activity in antigen processing and presentation”.

 

  • ESR14 Filippa Vasconcelos (Inocure, CZ) presented some results of her project “Development of Drug Delivery Systems for ERAP/IRAP Modulators”.

 

  • ESR12 Aroosha Raja (University Medical Center Utrecht, NL) kindly provided us with a few updated points about her research project dealing with “Transcriptional profiling of ERAPs in human blood dendritic cells (mDCs and pDCs) in different immune-related diseases”.

 

  • ESR11 Sandra Llamas Rizo (University of Athens, GR) presented some early results of her project entitled “Design, synthesis, and evaluation of phosphinic transition-state analogues of ERAP/IRAP”.

ESR words

The scientific training week provided us with a versatile toolbox in order to approach the ERAP/IRAP antigen processing from an immunological, structural and genomic aspect. This valuable piece of knowledge can be integrated into each ESR’s research project and improve experimental outcomes as well as interpretation of the observed artifacts. Notable examples of useful scientific bridging were: mechanistic and quantitative biological data, structural and conformational alterations during protein-ligand interactions, genomic databases and how to investigate them. Additionally, we had the pleasure to follow preliminary results from fellow ESR projects and have a first touch with their respective fields, while anticipation and excitement about the upcoming physical gathering in Rome could not be hidden.

   "I am beyond happy to have attended all these enlightening speeches from distinguished scientists in the field of antigen presentation and to have gained an insight in some of the ongoing projects within the consortium! " Martha (ESR4)