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Harvard medical school

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J. Clin. Invest., Nov 07 2023, e170512 | https://doi.org/10.1172/JCI170512 A narrow T cell receptor repertoire instructs thymic differentiation of MHC class Ib-restricted CD8+ regulatory T-cells

Hye-Jung Kim^1,2,*,†, Hidetoshi Nakagawa^1,2,*,‡, John Y. Choi^3,4,*, Xuchun Che^1,¶, Andrew Divris¹, Qingshi Liu^1,5, Andrew E. Wight^1,2, Hengcheng Zhang⁴, Anis Saad⁴, Zhabiz Solhjou⁴, Christa Deban⁴, Jamil R. Azzi^{3,4,§,††}, Harvey Cantor^{1,2,§,††}

¹Department of Cancer Immunology & Virology, Dana Farber Cancer Institute, Boston, Massachusetts, USA.

²Department of Immunology, Harvard Medical School, Boston, Massachusetts, USA.

³Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.

⁴Transplant Research Center, Brigham and Women’s Hospital, Boston, Massachusetts, USA.

⁵Department of Immunology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China

^*,§equal contributions [author order was determined by the authors themselves]

^†currently: Department of Immunology Discovery, Genentech Inc., San Francisco, CA, USA

^‡currently: Department of Gastroenterology, Kanazawa University Hospital, Kanazawa University, Japan

^¶currently: Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China

^††Correspondence: Jamil R. Azzi, Harvey Cantor

Abstract

Although most CD8+ T-cells are equipped to kill infected or transformed cells, a subset may regulate immune responses and preserve self-tolerance. Here we describe a CD8 lineage that is instructed to differentiate into CD8 T regulatory cells (Treg) by a surprisingly restricted set of T-cell receptors (TCR) that recognize MHC-E (mouse Qa-1) and several dominant self-peptides. Recognition and elimination of pathogenic target cells that express these Qa-1self-peptide complexes selectively inhibits pathogenic antibody responses without generalized immune suppression. Immunization with synthetic agonist peptides that mobilize CD8 Treg in vivo efficiently inhibit anti-graft antibody responses and markedly prolong heart and kidney organ graft survival. Definition of TCR-dependent differentiation and target recognition by this lineage of CD8 Treg may open the way to new therapeutic approaches to inhibit pathogenic antibody responses.

논문정보

형식Research article
게재일2023년 11월 (BRIC 등록일 2024-03-12)
연구진국외 연구진
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