title: Characterization of the human CD4(+) T-cell repertoire specific for major histocompatibility class I-restricted antigens.
abstract: While CD4(+) T lymphocytes usually recognize antigens in the context of major histocompatibility (MHC) class II alleles, occurrence of MHC class-I restricted CD4(+) T cells has been reported sporadically. Taking advantage of a highly sensitive MHC tetramer-based enrichment approach allowing detection and isolation of scarce Ag-specific T cells, we performed a systematic comparative analysis of HLA-A*0201-restricted CD4(+) and CD8(+) T-cell lines directed against several immunodominant viral or tumoral antigens. CD4(+) T cells directed against every peptide-MHC class I complexes tested were detected in all donors. These cells yielded strong cytotoxic and T helper 1 cytokine responses when incubated with HLA-A2(+) target cells carrying the relevant epitopes. HLA-A2-restricted CD4(+) T cells were seldom expanded in immune HLA-A2(+) donors, suggesting that they are not usually engaged in in vivo immune responses against the corresponding peptide-MHC class I complexes. However, these T cells expressed TCR of very high affinity and were expanded following ex vivo stimulation by relevant tumor cells. Therefore, we describe a versatile and efficient strategy for generation of MHC class-I restricted T helper cells and high affinity TCR that could be used for adoptive T-cell transfer- or TCR gene transfer-based immunotherapies.
authors: Inserm, U892, Nantes, France.
authors: François
authors: F
authors: Legoux
authors: Laetitia
authors: L
authors: Gautreau
authors: Leslie
authors: L
authors: Hesnard
authors: Alexandra
authors: A
authors: Leger
authors: Melinda
authors: M
authors: Moyon
authors: Marie-Claire
authors: MC
authors: Devilder
authors: Marc
authors: M
authors: Bonneville
authors: Xavier
authors: X
authors: Saulquin
mesh_terms: D000951:Antigens, Neoplasm / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D015789:HLA-A2 Antigen / Q000276:immunology*; D006801:Humans; D008297:Male; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D000956:Antigens, Viral; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D011948:Receptors, Antigen, T-Cell
keywords: CD4+ T cells; Human; Major histocompatibility (MHC); T‐cell receptor