Thread by @vipintukur

#SARS2 can readily alter its Spike protein via a single Amino acid substitution so that it is not recognized by CD8 T cells targeting the most prevalent epitope in Spike restricted by the most common HLA-I across the population. 1/

The Spike #P272L mutation that has arisen in at least 112 different #SARS2 lineages to date, including in lineages classified as “VOC”, was not recognized by the large CD8 T cell 2/

The CD8 T cells response seen across cohorts of HLA A∗02+ convalescent patients & individuals vaccinated against SARS2, despite these responses comprising of over 175 different individual T cell receptors. 3/

Viral escape at prevalent T cell epitopes restricted by high frequency HLAs may be particularly problematic when vaccine immunity is focused on a single protein such as SARS2 Spike 4/

This observation provides a strong argument for inclusion of multiple viral proteins in next generation vaccines & highlighting the need for monitoring T cell escape in new SARS2 variants.
5/

While it is not possible to directly attribute the emergence and propagation of the Spike #P272L SARS2 variant in parts of the world where HLA A∗02:01 is frequently expressed to CD8 T cell-mediated selection pressure………6/

…specific focusing of immune protection on a single protein (e.g. SARS2 Spike) favored by all currently approved vaccines is likely to enhance any tendency for escape at predominant T cell epitopes like YLQPRTFLL. 7/

Mutations that evade immunodominant T cell responses through population-frequent HLA can readily arise & disseminate, it will be prudent to monitor such occurrences & to increase breadth of next generation vaccines to incorporate other viral proteins 8/

cell.com/cell/fulltext/…