期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 43, 期 12, 页码 3244-3253出版社
WILEY-BLACKWELL
DOI: 10.1002/eji.201343726
关键词
CD4(+) T cells; Human; Major histocompatibility (MHC); T-cell receptor
类别
资金
- Agence Nationale de la Recherche sur le SIDA (ANRS) [R10102NN]
- Agence Nationale de la Recherche (ANR) [A05130GS]
- IHU CESTI (Centre Europeen pour les Sciences de la Transplantation et l'Immunotherapie)
- INSERM
- Universite de Nantes
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.
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