The cytoplasmic domain of MHC class I (MHC-I) molecules contains a single, highly conserved tyrosine residue (Y320). In previous work, we found that mice expressing a Y320F-mutated form of H-2Kb had reduced capacity to generate Kb-restricted cytotoxic T lymphocyte (CTL) responses following viral infection, due (at least in part) to defects in endolysosomal trafficking of H-2Kb and antigen cross-presentation by dendritic cells (DCs). In this study, we investigated whether there are additional, post-presentation dependencies on Y320 for T-cell priming. We engineered both human- and mouse-derived antigen-presenting cells (APCs) to express either wild-type MHC-I or variants of MHC-I containing Y320F or Y320E mutations. We found that Y320E-mutated HLA-A*0201 elicited enhanced in vitro priming and expansion of human antigen-specific CD8+ T-cells, which showed a unique transcriptional profile compared to T cells primed with APCs expressing either WT or Y320F-mutated A*0201. Furthermore, the Y320E variant of H-2Kb expressed in the context of a murine DC vaccine model induced altered T-cell differentiation kinetics while improving both anti-tumor immunity and augmenting the magnitude of memory CD8+ T cell responses in vivo. These results suggest that Y320 phosphorylation of MHC-I may play a role in determining the fate and function of CD8+ T cells and suggest a novel strategy for improving DC-based cancer immunotherapies.
","abstract_html":"<p>The cytoplasmic domain of MHC class I (MHC-I) molecules contains a single, highly conserved tyrosine residue (Y320). In previous work, we found that mice expressing a Y320F-mutated form of H-2K<sup>b</sup> had reduced capacity to generate K<sup>b</sup>-restricted cytotoxic T lymphocyte (CTL) responses following viral infection, due (at least in part) to defects in endolysosomal trafficking of H-2K<sup>b</sup> and antigen cross-presentation by dendritic cells (DCs). In this study, we investigated whether there are additional, post-presentation dependencies on Y320 for T-cell priming. We engineered both human- and mouse-derived antigen-presenting cells (APCs) to express either wild-type MHC-I or variants of MHC-I containing Y320F or Y320E mutations. We found that Y320E-mutated HLA-A*0201 elicited enhanced <em>in vitro</em> priming and expansion of human antigen-specific CD8<sup>+</sup> T-cells, which showed a unique transcriptional profile compared to T cells primed with APCs expressing either WT or Y320F-mutated A*0201. Furthermore, the Y320E variant of H-2K<sup>b</sup> expressed in the context of a murine DC vaccine model induced altered T-cell differentiation kinetics while improving both anti-tumor immunity and augmenting the magnitude of memory CD8<sup>+</sup> T cell responses <em>in vivo</em>. These results suggest that Y320 phosphorylation of MHC-I may play a role in determining the fate and function of CD8<sup>+</sup> T cells and suggest a novel strategy for improving DC-based cancer immunotherapies.</p>","abstract_has_math":false,"creators":["Sun, Yimo","Lizee, Gregory A","Tang, Yitao","Ortiz, Priscilla","Eric Davis, R","https://orcid.org/0000-0001-9555-4476
"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Dissertation (PhD)","degree_discipline":null,"degree_department":null,"school":null,"contributors":["Eric Davis","Greg Lizee","Cassian Yee"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2025,"date_issued":"2025-05-01T07:00:00Z","date_published":"2025-05-01T07:00:00Z","updated_at":"2026-07-24T05:50:31Z","subjects":["MHC class I","Human Leukocyte Antigen (HLA)","cytotoxic T cells","dendritic cells","tyrosine phosphorylation","cytoplasmic tail","Immunity","Immunotherapy","Other Immunology and Infectious Disease"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://digitalcommons.library.tmc.edu/utgsbs_dissertations/1452","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Eric Davis","Greg Lizee","Cassian Yee"]},{"key":"dc:creator","label":"Author","values":["Sun, Yimo","Lizee, Gregory A","Tang, Yitao","Ortiz, Priscilla","Eric Davis, R","https://orcid.org/0000-0001-9555-4476
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"]},{"key":"dc:title","label":"Title","values":["MHC Class I Tyrosine Phosphorylation Site Y320 Augments CD8+ T Cell Priming, Effector Function, and Memory Response"]}]}],"canonical_facts":{"dc:contributor":["Eric Davis","Greg Lizee","Cassian Yee"],"dc:creator":["Sun, Yimo","Lizee, Gregory A","Tang, Yitao","Ortiz, Priscilla","Eric Davis, R","https://orcid.org/0000-0001-9555-4476
"],"dc:date.available":["2025-10-31T07:00:00Z"],"dc:description.abstract":["The cytoplasmic domain of MHC class I (MHC-I) molecules contains a single, highly conserved tyrosine residue (Y320). In previous work, we found that mice expressing a Y320F-mutated form of H-2Kb had reduced capacity to generate Kb-restricted cytotoxic T lymphocyte (CTL) responses following viral infection, due (at least in part) to defects in endolysosomal trafficking of H-2Kb and antigen cross-presentation by dendritic cells (DCs). In this study, we investigated whether there are additional, post-presentation dependencies on Y320 for T-cell priming. We engineered both human- and mouse-derived antigen-presenting cells (APCs) to express either wild-type MHC-I or variants of MHC-I containing Y320F or Y320E mutations. We found that Y320E-mutated HLA-A*0201 elicited enhanced in vitro priming and expansion of human antigen-specific CD8+ T-cells, which showed a unique transcriptional profile compared to T cells primed with APCs expressing either WT or Y320F-mutated A*0201. Furthermore, the Y320E variant of H-2Kb expressed in the context of a murine DC vaccine model induced altered T-cell differentiation kinetics while improving both anti-tumor immunity and augmenting the magnitude of memory CD8+ T cell responses in vivo. These results suggest that Y320 phosphorylation of MHC-I may play a role in determining the fate and function of CD8+ T cells and suggest a novel strategy for improving DC-based cancer immunotherapies.
"],"dc:identifier":["https://digitalcommons.library.tmc.edu/utgsbs_dissertations/1452"],"dc:subject":["MHC class I","Human Leukocyte Antigen (HLA)","cytotoxic T cells","dendritic cells","tyrosine phosphorylation","cytoplasmic tail","Immunity","Immunotherapy","Other Immunology and Infectious Disease"],"dc:title":["MHC Class I Tyrosine Phosphorylation Site Y320 Augments CD8+ T Cell Priming, Effector Function, and Memory Response"],"thesis:degree_level":["Dissertation (PhD)"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T05:50:31Z"}