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This scenario highlights the complexity of predicting drug hypersensitivity reaction risk without considering additional factors. Furthermore, conducting prospective clinical studies of drug hypersensitivity reactions in humans is unfeasible. Therefore, this study aimed to prospectively evaluate HLA\u2010mediated drug hypersensitivity reactions by using a unique transgenic mouse line harbouring HLA\u2010B*57:01 (B*57:01\u2010Tg) and performing abacavir\u2010induced hypersensitivity reactions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      B*57:01\u2010Tg mice or their littermates were orally administered either an abacavir\u2010containing or a vehicle\u2010only diet. Subsequently, analyses were performed on isolated CD8\n                      <jats:sup>+<\/jats:sup>\n                      T\u2010cells collected from the lymph nodes, ear biopsies, or plasma of these mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      RNA sequencing and proteomic data analyses performed on the isolated CD8\n                      <jats:sup>+<\/jats:sup>\n                      T\u2010cells demonstrated that the expression levels of several glycolytic enzymes, including hexokinase 2, were significantly up\u2010regulated in abacavir\u2010treated B*57:01\u2010Tg mice. Moreover, the glycolytic rate and metabolite production significantly increased in these mice. Although treatment with the pyruvic acid carrier inhibitor UK5099 did not affect CD8\n                      <jats:sup>+<\/jats:sup>\n                      T\u2010cell activation, inhibiting glycolysis using 2\u2010deoxy\u2010D\u2010glucose or diet\u2010based calorie restriction attenuated the increase in IFN\u2010\u03b3\u2013secreting effector memory CD8\n                      <jats:sup>+<\/jats:sup>\n                      T\u2010cells. Consequently, this attenuation prevented CD8\n                      <jats:sup>+<\/jats:sup>\n                      T\u2010cell dermal infiltration in abacavir\u2010treated B*57:01\u2010Tg mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>\n                      Overall, these results suggest the indispensable role of glycolytic CD8\n                      <jats:sup>+<\/jats:sup>\n                      T\u2010cell metabolism in HLA\u2010mediated abacavir\u2010induced hypersensitivity reactions, which may further determine susceptibility to HLA\u2010mediated drug hypersensitivity reactions in humans.\n                    <\/jats:p>\n                  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