Structural definition of HLA class II-presented SARS-CoV-2 epitopes reveals a mechanism to escape pre-existing CD4+ T cell immunity

July 19, 2023

New study on CD4+ T cell epitopes of SARS-CoV-2 led by Dr Bruce MacLachlan is now published online in Cell Reports!

We define model antigens presented by HLA-DR1 and assess the impact of Spike mutations on T cell recognition. We aimed to provide high resolution epitope information of emerging CD4+ T cell epitopes and thus solved x-ray crystallographic structures of six peptide-HLA-DR1 complexes; 3 Spike and 3 non-Spike (M, nsp3 & nsp14). We could solve complexes of high and low affinity binding peptides and could not correlate peptide affinity with immunogenicity. 

As the pandemic unfolded, we observed Omicron mutations in two of the Spike epitopes we described structurally. Testing in HLA-DR1+ donors who had been vaccinated, we observed that donors could no longer recognise BA.1 Omicron variant forms. 

To understand this we solved further structures of Omicron variant peptide-HLA-DR1 complexes: observing a single amino acid mutation was sufficient to induce a drastic change in a presented epitope through inducing an epitope "register shift”. This effectively creating a "new" epitope to the perspective of T cells. 

This shows that CD4+ T cell memory is finely poised at the level of antigen presentation which is unique to the "open ended" nature of the HLA-II groove.

The full paper can be accessed here

Successful Immunotherapy is Linked to Devlopment of Specialised Blood Vessels in Solid Cancers

December 15th 2022

Applying three-dimensional imaging methods, researcher, Dr Stefan Milutinovic, showed that cancers which are successfully killed by the immune system contain networks of blood vessels which are specialised in their ability to allow immune cells to enter tumours. The work has just been published in Cancer Research Communications.

Prof Awen Gallimore said that the new technology offers the possibility to better understand the co-operation between blood vessels and immune activation and moreover, that the results indicate that targeting blood vessels has the potential to significantly improve the success of the current immunotherapies.

The lab, which is funded by Cancer Research UK, is currently building on this work to find ways of inducing development of these blood vessels in solid cancers.

Read the full paper here.