Memory CD4 T cells established by endemic human Coronaviruses have the potential to be recruited into the response to SARS-Cov-2

For centuries, humans have become infected with endemic circulating Coronaviruses (hCoV), typically repeatedly throughout life. To understand how these respiratory infections establish CD4 T cells memory and whether this memory has the potential to be recruited into the immune response to SARS-CoV-2, we studies human peripheral blood samples collected prior to 2019. Our studies revealed highly variable reactivity to the human coronavirus proteins, related both to the age of subjects and with regard to the functional potential, including cytotoxic activityl. Particularly striking was the diminished human CD4 memory to hCoV associated with age, in contrast to reactivity to influenza epitopes, studied in parallel. We also provide evidence that CD4 T cells reactive with the alpha hCoV can be cross boosted by the two lineages, based on accumulation of CD4 T cells specific for the highly conserved S2 domains of the spike proteins derived from these endemic viruses. Finally, we found that the human CD4 T cells elicited by the endemic hCoV are able to recognize SARS-CoV-2 epitopes and display functional potential linked to the specific viral antigen examined, particularly notable in the cytotoxic potential of the SARS CoV-2 reactive CD4 T cells.
 
Learning Objectives
 
1.     Understand the epidemiology of human Coronaviruses.
2.     Learn the types of human CD4 T cells elicited by human Coronaviruses.
3.     Understand the basis of cross-reactive T cell recognition of related viruses.