CD4+ T-cell-Mediated Rejection of MHC Class II-Positive Tumor Cells Is Dependent on Antigen Secretion and Indirect Presentation on Host APCs

Cancer Research
Ole Audun Werner HaabethAnders Tveita

Abstract

Tumor-specific CD4+ T cells have been shown to mediate efficient antitumor immune responses against cancer. Such responses can occur through direct binding to MHC class II (MHC II)-expressing tumor cells, or indirectly via activation of professional antigen-presenting cells (APC) that take up and present the tumor antigen. We have previously shown that CD4+ T cells reactive against an epitope within the Ig light chain variable region of a murine B-cell lymphoma can reject established tumors. Given the presence of MHC II molecules at the surface of lymphoma cells, we investigated whether MHC II-restricted antigen presentation on tumor cells alone was required for rejection. Variants of the A20 B lymphoma cell line that either secreted or intracellularly retained different versions of the tumor-specific antigen revealed that antigen secretion by the MHC II-expressing tumor cells was essential both for the priming and effector phase of CD4+ T-cell-driven antitumor immune responses. Consistent with this, genetic ablation of MHC II in tumor cells, both in the case of B lymphoma and B16 melanoma, did not preclude rejection of tumors by tumor antigen-specific CD4+ T cells in vivo These findings demonstrate that MHC class II expression...Continue Reading

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Citations

Oct 9, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kenneth H BuetowK Taraszka Hastings
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