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SARS-CoV-2 antigen exposure history shapes phenotypes and specificity of memory CD8+ T cells

2022; Nature Portfolio; Volume: 23; Issue: 5 Linguagem: Inglês

10.1038/s41590-022-01184-4

1529-2916

Anastasia A. Minervina, Mikhail V. Pogorelyy, Allison M. Kirk, Jeremy Chase Crawford, E. Kaitlynn Allen, Ching‐Heng Chou, Robert C. Mettelman, Kim Allison, Chun-Yang Lin, David C. Brice, Zhu Xun, Kasi Vegesana, Gang Wu, Sanchit Trivedi, Pratibha Kottapalli, Daniel Darnell, Suzanne McNeely, Scott R. Olsen, Stacey Schultz‐Cherry, Jeremie H. Estepp, Aditya H. Gaur, James E. Hoffman, Motomi Mori, Li Tang, Elaine Tuomanen, Richard J. Webby, Hana Hakim, Randall T. Hayden, Diego R. Hijano, Resha Bajracharya, Walid H. Awad, Lee-Ann Van de Velde, Brandi L. Clark, Taylor L. Wilson, Aisha Souquette, Ashley Castellaw, Ronald H. Dallas, Jason Hodges, Ashleigh Gowen, Jamie Russell-Bell, James Sparks, David E. Wittman, Thomas Fabrizio, Sean Cherry, Ericka Kirkpatrick Roubidoux, Valerie Cortez, Pamela Freiden, Nicholas Wohlgemuth, Kendall Whitt, Maureen A. McGargill, Joshua Wolf, Paul G. Thomas,

COVID-19 epidemiological studies

Although mRNA vaccine efficacy against severe coronavirus disease 2019 remains high, variant emergence has prompted booster immunizations. However, the effects of repeated exposures to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens on memory T cells are poorly understood. Here, we utilize major histocompatibility complex multimers with single-cell RNA sequencing to profile SARS-CoV-2-responsive T cells ex vivo from humans with one, two or three antigen exposures, including vaccination, primary infection and breakthrough infection. Exposure order determined the distribution between spike-specific and non-spike-specific responses, with vaccination after infection leading to expansion of spike-specific T cells and differentiation to CCR7−CD45RA+ effectors. In contrast, individuals after breakthrough infection mount vigorous non-spike-specific responses. Analysis of over 4,000 epitope-specific T cell antigen receptor (TCR) sequences demonstrates that all exposures elicit diverse repertoires characterized by shared TCR motifs, confirmed by monoclonal TCR characterization, with no evidence for repertoire narrowing from repeated exposure. Our findings suggest that breakthrough infections diversify the T cell memory repertoire and current vaccination protocols continue to expand and differentiate spike-specific memory. Thomas and colleagues describe how multiple SARS-CoV-2 antigen exposures, including mRNA vaccine boosters, primary infection and breakthrough infection, shape T cell immunity.