A blend of broadly-reactive and pathogen-selected Vγ4 Vδ1 T cell receptors confer broad bacterial reactivity of resident memory γδ T cells

Camille Khairallah, Julie A. Bettke, Oleksandr Gorbatsevych, Zhijuan Qiu, Yue Zhang, Kyungjin Cho, Kwang Soon Kim, Timothy H. Chu, Jessica N. Imperato, Shinya Hatano, Galina Romanov, Yasunobo Yoshikai, Lynn Puddington, Charles D. Surh, James B. Bliska, Adrianus W.M. van der Velden, Brian S. Sheridan

Research output: Contribution to journalArticlepeer-review

Abstract

Although murine γδ T cells are largely considered innate immune cells, they have recently been reported to form long-lived memory populations. Much remains unknown about the biology and specificity of memory γδ T cells. Here, we interrogated intestinal memory Vγ4 Vδ1 T cells generated after foodborne Listeria monocytogenes (Lm) infection to uncover an unanticipated complexity in the specificity of these cells. Deep TCR sequencing revealed that a subset of non-canonical Vδ1 clones are selected by Lm infection, consistent with antigen-specific clonal expansion. Ex vivo stimulations and in vivo heterologous challenge infections with diverse pathogenic bacteria revealed that Lm-elicited memory Vγ4 Vδ1 T cells are broadly reactive. The Vγ4 Vδ1 T cell recall response to Lm, Salmonella enterica serovar Typhimurium (STm) and Citrobacter rodentium was largely mediated by the γδTCR as internalizing the γδTCR prevented T cell expansion. Both broadly-reactive canonical and pathogen-selected non-canonical Vδ1 clones contributed to memory responses to Lm and STm. Interestingly, some non-canonical γδ T cell clones selected by Lm infection also responded after STm infection, suggesting some level of cross-reactivity. These findings underscore the promiscuous nature of memory γδ T cells and suggest that pathogen-elicited memory γδ T cells are potential targets for broad-spectrum anti-infective vaccines.

Original languageEnglish
JournalMucosal Immunology
DOIs
Publication statusAccepted/In press - 2021

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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