TY - JOUR
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 - Publisher Copyright:
© 2023 Institut Pasteur
PY - 2023/11/1
Y1 - 2023/11/1
N2 - 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.
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
UR - http://www.scopus.com/inward/record.url?scp=85172869585&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85172869585&partnerID=8YFLogxK
U2 - 10.1016/j.micinf.2023.105182
DO - 10.1016/j.micinf.2023.105182
M3 - Article
C2 - 37423326
AN - SCOPUS:85172869585
SN - 1286-4579
VL - 25
JO - Microbes and Infection
JF - Microbes and Infection
IS - 8
M1 - 105182
ER -