6533b82efe1ef96bd12932d6

RESEARCH PRODUCT

Cooperation of Human Tumor-Reactive CD4+ and CD8+ T Cells after Redirection of Their Specificity by a High-Affinity p53A2.1-Specific TCR

Jürgen KuballLinda A. ShermanMatthias TheobaldRenate EngelEdite Antunes FerreiraPedro RomeroRalf-holger VossFrank SchmitzPhilippe GuillaumeSusanne StrandChristoph Huber

subject

CD4-Positive T-LymphocytesT cellImmunologyReceptors Antigen T-CellMice TransgenicT-Cell Antigen Receptor SpecificityCD8-Positive T-LymphocytesBiologyMiceInterleukin 21Transduction GeneticTumor Cells CulturedmedicineAnimalsHumansImmunology and AllergyCytotoxic T cellCloning MolecularAntigen-presenting cellT-cell receptorFlow CytometryNatural killer T cellCell biologyCTL*Infectious Diseasesmedicine.anatomical_structureImmunologyTumor Suppressor Protein p53CD8T-Lymphocytes Cytotoxic

description

Abstract Efficient immune attack of malignant disease requires the concerted action of both CD8 + CTL and CD4 + Th cells. We used human leukocyte antigen (HLA)-A*0201 (A2.1) transgenic mice, in which the mouse CD8 molecule cannot efficiently interact with the α3 domain of A2.1, to generate a high-affinity, CD8-independent T cell receptor (TCR) specific for a commonly expressed, tumor-associated cytotoxic T lymphocyte (CTL) epitope derived from the human p53 tumor suppressor protein. Retroviral expression of this CD8-independent, p53-specific TCR into human T cells imparted the CD8 + T lymphocytes with broad tumor-specific CTL activity and turned CD4 + T cells into potent tumor-reactive, p53A2.1-specific Th cells. Both T cell subsets were cooperative and interacted synergistically with dendritic cell intermediates and tumor targets. The intentional redirection of both CD4 + Th cells and CD8 + CTL by the same high-affinity, CD8-independent, tumor-specific TCR could provide the basis for novel broad-spectrum cancer immunotherapeutics.

yearjournalcountryeditionlanguage
2004-06-22Immunity
https://doi.org/10.1016/j.immuni.2004.12.005