A Coreceptor-Independent Transgenic Human TCR Mediates Anti-Tumor and Anti-Self Immunity in Mice

摘要: Recent advancements in T cell immunotherapy suggest that cells engineered with high-affinity TCR can offer better tumor regression. However, whether a alone is sufficient to control growth, or the subset bearing also important remains unclear. Using human tyrosinase epitope-reactive, CD8-independent, isolated from MHC class I-restricted CD4(+) obtained tumor-infiltrating lymphocytes (TIL) of metastatic melanoma patient, we developed novel transgenic mouse C57BL/6 background. This HLA-A2-restricted was positively selected on both and CD8(+) single-positive cells. when HLA-A2 background, primarily expressed by CD3(+)CD4(-)CD8(-) double-negative TIL 1383I CD4(+), CD8(+), CD4(-)CD8(-) were functional retained ability growth without need for vaccination cytokine support vivo. Furthermore, HLA-A2(+)/human double-transgenic mice spontaneous hair depigmentation had visual defects progressed age. Our data show expression CD3(+) murine melanoma, presence absence CD4 CD8 coreceptors little effect its capacity.