title: A similarity in peptide cross-reactivity between alloantigen- and nominal antigen-induced CD8+ T cell responses in vitro.
abstract: Raising tumor-specific allorestricted T cells in vitro for adoptive transfusion is expected to circumvent host tumor tolerance. However, it has been assumed that alloreactive T cell clones activated in vitro ranges from peptide-specific with high avidity to peptide-degenerate with low avidity. In this study, we examined the peptide specificity and cross-reactivity of T cell responses in vitro to an allogeneic epitope and a nominal epitope with a modified co-culture of lymphocytes and autologous monocytes. After binding to the monocyte via the interaction of its Fc part and the cell surface IgG Fc receptor type I (FcγRI), a fusion protein consisting of the extracellular domains of HLA-A2 molecule and the Fc region of IgG1 (the dimer) introduced a single epitope into the co-culture. The dimer-coated monocytes stimulated the proliferation of autologous CD8(+) T cells after co-culturing. The CD8(+) T cell responses were self-HLA-restricted for HLA-A2-positive (HLA-A2+ve) samples and allo-HLA-restricted for HLA-A2-negative (HLA-A2-ve) samples, since the co-cultural bulks stained with HLA-A2 tetramers, human interferon-gamma (IFN-γ) production in response to T cell receptor (TCR) ligands, and cytotoxicity against a panel of target cells exhibited peptide-specific properties. Two HLA-A2-restricted peptides with sequence homology were included, allowing the comparison of cross-reactivity between allo-antigen- and nominal antigen-induced CD8(+) T cell responses. Interestingly, the allo- and self-HLA-restricted CD8(+) T cell responses were similar in the peptide cross-reactivity, although the allorestricted T cell response seemed, overall, more intensive and had higher binding affinity to specific tetramer. Our findings indicated the alloreactive T cells raised by the co-culture in vitro were as peptide specific and cross-reactive as the self-HLA-restricted ones.
authors.affiliation: Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Yu
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Lichen
authors.initials: L
authors.lastname: Ouyang
authors.forename: Yeli
authors.initials: Y
authors.lastname: Gong
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Liang
authors.forename: Guanxin
authors.initials: G
authors.lastname: Shen
authors.forename: Xiufang
authors.initials: X
authors.lastname: Weng
authors.forename: Xiongwen
authors.initials: X
authors.lastname: Wu
mesh_terms: D000951:Antigens, Neoplasm / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic; D019281:Dimerization; D015488:HIV Antigens / Q000276:immunology; D015789:HLA-A2 Antigen / Q000276:immunology; D018936:Hepatitis C Antigens / Q000276:immunology; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000276:immunology; D059425:Interferon-gamma Release Tests; D007519:Isoantigens / Q000276:immunology*; D008213:Lymphocyte Activation; D009000:Monocytes / Q000276:immunology; D014442:Monophenol Monooxygenase / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology*; D037182:T-Cell Antigen Receptor Specificity; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D017361:Viral Nonstructural Proteins / Q000276:immunology; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000276:immunology; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000951:Antigens, Neoplasm; D015488:HIV Antigens; D015789:HLA-A2 Antigen; D018936:Hepatitis C Antigens; D007141:Immunoglobulin Fc Fragments; D007519:Isoantigens; D014442:Monophenol Monooxygenase; D010446:Peptide Fragments; D017361:Viral Nonstructural Proteins; D054311:nef Gene Products, Human Immunodeficiency Virus; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C514837:nef protein, Human immunodeficiency virus 1