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A blend of broadly-reactive and pathogen-selected V gamma 4 V delta 1 T cell receptors confer broad bacterial reactivity of resident memory gamma delta T cells

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Title
A blend of broadly-reactive and pathogen-selected V gamma 4 V delta 1 T cell receptors confer broad bacterial reactivity of resident memory gamma delta T cells
Author(s)
Khairallah, Camille; Bettke, Julie A.; Gorbatsevych, Oleksandr; Qiu, Zhijuan; Zhang, Yue; Cho, Kyungjin; Kim, Kwang Soon; Chu, Timothy H.; Imperato, Jessica N.; Hatano, Shinya; Romanov, Galina; Yoshikai, Yasunobo; Puddington, Lynn; Surh, Charles D.; Bliska, James B.; van der Velden, Adrianus W. M.; Sheridan, Brian S.
Publication Date
2021-01
Journal
MUCOSAL IMMUNOLOGY
Publisher
SPRINGERNATURE
Abstract
Although murine gamma delta 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 gamma delta T cells. Here, we interrogated intestinal memory V gamma 4 V delta 1 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 V delta 1 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 V gamma 4 V delta 1 T cells are broadly reactive. The V gamma 4 V delta 1 T cell recall response to Lm, Salmonella enterica serovar Typhimurium (STm) and Citrobacter rodentium was largely mediated by the gamma delta TCR as internalizing the gamma delta TCR prevented T cell expansion. Both broadly-reactive canonical and pathogen-selected non-canonical V delta 1 clones contributed to memory responses to Lm and STm. Interestingly, some non-canonical gamma delta 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 gamma delta T cells and suggest that pathogen-elicited memory gamma delta T cells are potential targets for broad-spectrum anti-infective vaccines.
URI
https://pr.ibs.re.kr/handle/8788114/10399
DOI
10.1038/s41385-021-00447-x
ISSN
1933-0219
Appears in Collections:
Academy of Immunology and Microbiology(면역 미생물 공생 연구단) > 1. Journal Papers (저널논문)
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