title: Extracellular domains of CD8α and CD8ß subunits are sufficient for HLA class I restricted helper functions of TCR-engineered CD4(+) T cells.
abstract: By gene transfer of HLA-class I restricted T-cell receptors (TCRs) (HLA-I-TCR) into CD8(+) as well as CD4(+) T-cells, both effector T-cells as well as helper T-cells can be generated. Since most HLA-I-TCRs function best in the presence of the CD8 co-receptor, the CD8αß molecule has to be co-transferred into the CD4(+) T-cells to engineer optimal helper T-cells. In this study, we set out to determine the minimal part of CD8αβ needed for optimal co-receptor function in HLA-I-TCR transduced CD4(+) T-cells. For this purpose, we transduced human peripheral blood derived CD4(+) T-cells with several HLA-class I restricted TCRs either with or without co-transfer of different CD8 subunits. We demonstrate that the co-transduced CD8αβ co-receptor in HLA-I-TCR transduced CD4(+) T-cells behaves as an adhesion molecule, since for optimal antigen-specific HLA class I restricted CD4(+) T-cell reactivity the extracellular domains of the CD8α and ß subunits are sufficient.
authors.affiliation: Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands. m.m.van_loenen@lumc.nl
authors.forename: Marleen M
authors.initials: MM
authors.lastname: van Loenen
authors.forename: Renate S
authors.initials: RS
authors.lastname: Hagedoorn
authors.forename: Renate
authors.initials: R
authors.lastname: de Boer
authors.forename: J H Frederik
authors.initials: JH
authors.lastname: Falkenburg
authors.forename: Mirjam H M
authors.initials: MH
authors.lastname: Heemskerk
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D016827:CD8 Antigens / Q000737:chemistry / Q000378:metabolism*; D060846:Cell Engineering / Q000379:methods*; D005110:Extracellular Space / Q000378:metabolism; D006680:HLA Antigens / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism*; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology*; D014162:Transfection
chemical_list: D016827:CD8 Antigens; C431698:CD8alpha antigen; C477867:CD8beta antigen; D006680:HLA Antigens; D021122:Protein Subunits; D011948:Receptors, Antigen, T-Cell; D007371:Interferon-gamma