# Coronavirus replicase epitopes induce cross-reactive CD8 T cell responses in SARS-CoV-2-naive people with HIV-1

## TL;DR

The study found that people with HIV who have not been infected by SARS-CoV-2 still have T cells that react to common cold coronaviruses, which may influence their immunity to SARS-CoV-2.

## Contribution

The study identifies cross-reactive CD8 T cell epitopes in SARS-CoV-2 replicase and links HLA-I alleles to differences in SARS-CoV-2 susceptibility.

## Key findings

- Replicase peptides induced IFN-γ responses in 63% of SARS-CoV-2-naïve individuals.
- A functional TCR for the HLA-B∗35:03-restricted epitope CoV-YL8 was identified.
- HLA-B∗35:01 and HLA-C∗04 increase SARS-CoV-2 susceptibility, while HLA-C∗07 is protective.

## Abstract

Cross-reactive T cell immunity between common cold coronaviruses and SARS-CoV-2 may influence COVID-19 susceptibility. To identify cross-reactive CD8 T cell epitopes, we analyzed responses to 21 homologous SARS-CoV-2 replicase peptides in 177 people living with HIV (PLWH) on antiretroviral therapy, of which 133 did not have prior SARS-CoV-2 infection. Replicase peptides induced IFN-γ responses in 63% of the SARS-CoV-2-naïve individuals and in 73% of individuals with prior SARS-CoV-2-infection. We could define several cross-reactive epitopes, including the HLA-B∗35:03 restricted CoV-YL8, and characterized a CoV-YL8-specific T cell receptor cloned from a SARS-CoV-2 seronegative individual. Analysis of the association between HLA-I alleles and SARS-CoV-2 infections over a 16-months period revealed that in a cohort of 452 PLWH, HLA-B∗35:03 and C∗07 were underrepresented in the 55 persons with a history of SARS-CoV-2 infection while HLA-B∗35:01 and HLA-C∗04 were associated with a higher infection rate. Taken together, our study suggests an HLA-I-mediated effect of common cold coronaviruses on SARS-CoV-2 immunity.

•SARS-CoV-2 replicase cross-reactive T cells are frequent in SARS-CoV-2 naive PLWH•A functional TCR for the B∗35:03-restricted replicase epitope YL8 was identified•While HLA-B∗35 and C∗04 increase SARS-CoV-2 susceptibility, C∗07 is protective•HLA-B∗35:01 and 35:03 subtypes have diverging effects on SARS-CoV-2 susceptibility

SARS-CoV-2 replicase cross-reactive T cells are frequent in SARS-CoV-2 naive PLWH

A functional TCR for the B∗35:03-restricted replicase epitope YL8 was identified

While HLA-B∗35 and C∗04 increase SARS-CoV-2 susceptibility, C∗07 is protective

HLA-B∗35:01 and 35:03 subtypes have diverging effects on SARS-CoV-2 susceptibility

Health sciences; Medicine; Medical specialty; Immunology; Virology