Immunization with the amino-terminus region of dense granule protein 6 (GRA6) of Toxoplasma gondii activates CD8+ cytotoxic T cells capable of removing tissue cysts of the parasite through antigen presentation by human HLA-A2.1

Rajesh Mani; Corinne Mercier; Marie France Delauw; Yasuhiro Suzuki

doi:10.1016/j.micinf.2023.105182

Immunization with the amino-terminus region of dense granule protein 6 (GRA6) of Toxoplasma gondii activates CD8⁺ cytotoxic T cells capable of removing tissue cysts of the parasite through antigen presentation by human HLA-A2.1

Rajesh Mani, Corinne Mercier, Marie France Delauw, Yasuhiro Suzuki

Research output: Contribution to journal › Article › peer-review

Abstract

CD8⁺ T cells from HLA-A2.1-transgenic mice, but not wild-type mice, immunized with the amino-terminus region (aa 41–152) of dense granule protein 6 (GRA6Nt) of Toxoplasma gondii secreted large amounts of perforin and granzyme B in response to GRA6Nt through antigen presentation by HLA-A2.1 in vitro. When those CD8⁺ T cells were transferred into chronically infected HLA-A2.1-expressing NSG mice deficient in T cells, cerebral cyst burden of the recipients of HLA-A2.1-transgenic T cells, but not of WT T cells, became significantly less than that of control mice with no cell transfer. Furthermore, the significant reduction of the cyst burden by a transfer of the HLA-A2.1-transgenic CD8⁺ immune T cells required an expression of HLA-A2.1 in the recipient NSG mice. Thus, antigen presentation of GRA6Nt by human HLA-A2.1is able to activate anti-cyst CD8⁺ T cells that eliminate T. gondii cysts through antigen presentation by human HLA-A2.1.

Original language	English
Article number	105182
Journal	Microbes and Infection
DOIs	https://doi.org/10.1016/j.micinf.2023.105182
State	Accepted/In press - 2023

Bibliographical note

Funding Information:
The studies are supported in part by the National Institutes of Health , the United States (NIH) grants ( AI095032 , AI152597 , AI136821 , and AI134323 ) (Y.S.). The authors appreciate the support from the Protein Core Laboratory of the University of Kentucky College of Medicine, United States for production and purification of rGRA6Nt.

Funding Information:
The studies are supported in part by the National Institutes of Health, the United States (NIH) grants (AI095032, AI152597, AI136821, and AI134323) (Y.S.). The authors appreciate the support from the Protein Core Laboratory of the University of Kentucky College of Medicine, United States for production and purification of rGRA6Nt.

Publisher Copyright:
© 2023 Institut Pasteur

Keywords

CD8 T cells
Dense granule protein 6
HLA-A2
Protective immunity
Tissue cysts
Toxoplasma

ASJC Scopus subject areas

Microbiology
Immunology
Infectious Diseases

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Mani, R., Mercier, C., Delauw, M. F., & Suzuki, Y. (Accepted/In press). Immunization with the amino-terminus region of dense granule protein 6 (GRA6) of Toxoplasma gondii activates CD8⁺ cytotoxic T cells capable of removing tissue cysts of the parasite through antigen presentation by human HLA-A2.1. Microbes and Infection, Article 105182. https://doi.org/10.1016/j.micinf.2023.105182

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title = "Immunization with the amino-terminus region of dense granule protein 6 (GRA6) of Toxoplasma gondii activates CD8+ cytotoxic T cells capable of removing tissue cysts of the parasite through antigen presentation by human HLA-A2.1",

abstract = "CD8+ T cells from HLA-A2.1-transgenic mice, but not wild-type mice, immunized with the amino-terminus region (aa 41–152) of dense granule protein 6 (GRA6Nt) of Toxoplasma gondii secreted large amounts of perforin and granzyme B in response to GRA6Nt through antigen presentation by HLA-A2.1 in vitro. When those CD8+ T cells were transferred into chronically infected HLA-A2.1-expressing NSG mice deficient in T cells, cerebral cyst burden of the recipients of HLA-A2.1-transgenic T cells, but not of WT T cells, became significantly less than that of control mice with no cell transfer. Furthermore, the significant reduction of the cyst burden by a transfer of the HLA-A2.1-transgenic CD8+ immune T cells required an expression of HLA-A2.1 in the recipient NSG mice. Thus, antigen presentation of GRA6Nt by human HLA-A2.1is able to activate anti-cyst CD8+ T cells that eliminate T. gondii cysts through antigen presentation by human HLA-A2.1.",

keywords = "CD8 T cells, Dense granule protein 6, HLA-A2, Protective immunity, Tissue cysts, Toxoplasma",

author = "Rajesh Mani and Corinne Mercier and Delauw, {Marie France} and Yasuhiro Suzuki",

note = "Funding Information: The studies are supported in part by the National Institutes of Health , the United States (NIH) grants ( AI095032 , AI152597 , AI136821 , and AI134323 ) (Y.S.). The authors appreciate the support from the Protein Core Laboratory of the University of Kentucky College of Medicine, United States for production and purification of rGRA6Nt. Funding Information: The studies are supported in part by the National Institutes of Health, the United States (NIH) grants (AI095032, AI152597, AI136821, and AI134323) (Y.S.). The authors appreciate the support from the Protein Core Laboratory of the University of Kentucky College of Medicine, United States for production and purification of rGRA6Nt. Publisher Copyright: {\textcopyright} 2023 Institut Pasteur",

year = "2023",

doi = "10.1016/j.micinf.2023.105182",

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Immunization with the amino-terminus region of dense granule protein 6 (GRA6) of Toxoplasma gondii activates CD8⁺ cytotoxic T cells capable of removing tissue cysts of the parasite through antigen presentation by human HLA-A2.1. / Mani, Rajesh; Mercier, Corinne; Delauw, Marie France et al.
In: Microbes and Infection, 2023.

Research output: Contribution to journal › Article › peer-review

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T1 - Immunization with the amino-terminus region of dense granule protein 6 (GRA6) of Toxoplasma gondii activates CD8+ cytotoxic T cells capable of removing tissue cysts of the parasite through antigen presentation by human HLA-A2.1

AU - Mani, Rajesh

AU - Mercier, Corinne

AU - Delauw, Marie France

AU - Suzuki, Yasuhiro

N1 - Funding Information: The studies are supported in part by the National Institutes of Health , the United States (NIH) grants ( AI095032 , AI152597 , AI136821 , and AI134323 ) (Y.S.). The authors appreciate the support from the Protein Core Laboratory of the University of Kentucky College of Medicine, United States for production and purification of rGRA6Nt. Funding Information: The studies are supported in part by the National Institutes of Health, the United States (NIH) grants (AI095032, AI152597, AI136821, and AI134323) (Y.S.). The authors appreciate the support from the Protein Core Laboratory of the University of Kentucky College of Medicine, United States for production and purification of rGRA6Nt. Publisher Copyright: © 2023 Institut Pasteur

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AB - CD8+ T cells from HLA-A2.1-transgenic mice, but not wild-type mice, immunized with the amino-terminus region (aa 41–152) of dense granule protein 6 (GRA6Nt) of Toxoplasma gondii secreted large amounts of perforin and granzyme B in response to GRA6Nt through antigen presentation by HLA-A2.1 in vitro. When those CD8+ T cells were transferred into chronically infected HLA-A2.1-expressing NSG mice deficient in T cells, cerebral cyst burden of the recipients of HLA-A2.1-transgenic T cells, but not of WT T cells, became significantly less than that of control mice with no cell transfer. Furthermore, the significant reduction of the cyst burden by a transfer of the HLA-A2.1-transgenic CD8+ immune T cells required an expression of HLA-A2.1 in the recipient NSG mice. Thus, antigen presentation of GRA6Nt by human HLA-A2.1is able to activate anti-cyst CD8+ T cells that eliminate T. gondii cysts through antigen presentation by human HLA-A2.1.

KW - CD8 T cells

KW - Dense granule protein 6

KW - HLA-A2

KW - Protective immunity

KW - Tissue cysts

KW - Toxoplasma

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