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Designing new High Affinity Peptide Ligands for HLA-DQ2 Using a Positional Scanning Peptide Library

A team of researchers recently to examine the design of new high affinity peptide ligands for HLA-DQ2 using a positional scanning peptide library.

The research team included U. Jüse, Y. van de Wal, F. Koning, L. M. Sollid, B. Fleckenstein with the Centre for Immune Regulation, Institute of Immunology, Oslo University Hospital-Rikshospitalet, Oslo, Norway.

HLA-DQ2 (DQA1*0501/DQB1*0201) is associated with several immune disorders including celiac disease, which results from an inappropriate T-cell response to gluten.

Researchers hope that interference with peptide presentation by HLA-DQ2, perhaps through the use of of peptide blockers, might lead to new treatment strategy for such HLA associated disorders. For such strategies to work, it will be necessary to identify ligands that bind much better to HLA-DQ2 than the disease related epitopes.

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The team used a positional scanning nonapeptide library to determine the optimal amino acids for each position of the HLA-DQ2 binding frame. By combining the optimal residues in each position, the team was able to design high affinity binders to HLA-DQ2.

Interestingly, the decapeptide with highest affinity was composed of the most favorable residues in each position. This sequence bound 50-fold better than the immunodominant gluten epitope DQ2-alpha-I-gliadin what makes it an interesting lead compound for the development of blockers.

The correlation between measured and predicted affinities was poorer for some natural HLA-DQ2 ligands, but notably these peptides did not have optimal amino acids at all positions.

The team's method offers a straightforward approach for developing high affinity binders to HLA class II molecules.

Source: Hum Immunol. 2010 Jan 24.

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JMG I have never laughed so hard! This was the best epic comment I've read! Thankyou so much! Your all teaching me so much! Love the 'my glass to go' idea!! I will be adopting this... can't believe the mucky glasses we must be drinking from! Shocking! Im still baffled how so many people don't understand cross contamination i.e. The crumbs on the work surface to cut the lime for your tasty beverage! Your all amazing Thankyou x

Yes! I never really had GI symptoms, but I did have palpitations and restless leg syndrome from anemia. These went away within the first month. But myalgia and joint aches aren't better after 1 year. Waiting to get my antibodies re-tested and see if they're negative.....

I will just share an experience I had..... I went to a steak house where there weren't a lot of safe options for me. So, I decided just to order a drink and eat later. I asked the bar tender about how they made their margaritas - fresh lime juice, fresh orange juice and gluten free tequila. gluten-free all the way. My husband went back to order for me and noticed that the bartender was juicing the limes and serving bread to the customers at the bar at the same time. I would have totally drank that margarita had he not seen him doing that. I decided to skip the margarita because of the high chance of CC

If you're going to continue to push for a diagnosis stay on gluten! A break could lead to a false negative. It's a lot harder to go off it and then go back on...

I still prefer steaming, but I wash my white rice throughly. I purchase California rice which has a lower level of arsenic. Moderation is key to most everything! ?