Scientists have developed a new technology to detect a wider variety of T cells that recognize coronaviruses, including SARS-CoV-2. The technology revealed that killer T cells capable of recognizing epitopes conserved across all coronaviruses are much more abundant in COVID-19 patients with mild disease versus those with more severe illness, suggesting a protective role for these broad-affinity T cells. The ability to distinguish T cells based on their affinities to SARS-CoV-2 could help scientists elucidate the disparity in COVID-19 outcomes and determine which COVID-19 patients will or will not exhibit a successful immune response against the virus, the authors say. Their work improves upon the primary tool used to identify T cells - antigen tetramers bound to MHC - by instead attracting the cells to multimerized complexes of antigens bound to MHC called "spheromers." Because tetramers can harbor a maximum of four MHC-antigen complexes, they tend to miss T cells with a low affinity for certain antigens. Vamsee Mallajosyula and colleagues tackled these limitations with their spheromers, each of which simultaneously displays 12 copies of an individual peptide-MHC complex. The spheromer is easy to produce and compatible with currently available MHC molecules and tetramer components, allowing for easy adoption of their new protocol, the authors say. When applied to blood samples from COVID-19 patients and individuals not yet exposed to SARS-CoV-2, the spheromers stained specific T cells more efficiently and captured a more diverse repertoire of TCRs compared with the tetramer. Using the technology, the authors found that T cells capable of recognizing peptides conserved across all coronaviruses were more abundant and exhibited a "memory" phenotype - a desirable feature among T cells targeted by vaccines - compared with T cells that only recognize SARS-CoV-2. Indeed, COVID-19 patients with mild disease harbored a greater number of killer T cells with these conserved specificities than those with more severe illness, suggesting the broad-affinity T cells are protective, the authors say. Next steps will require enhancing the spheromer technology to include more MHC proteins, they add.
