Characterization of the human CD4(+) T-cell repertoire specific for major histocompatibility class I-restricted antigens.
Eur J Immunol
; 43(12): 3244-53, 2013 Dec.
Article
em En
| MEDLINE
| ID: mdl-23963968
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.
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Base de dados:
MEDLINE
Assunto principal:
Receptores de Antígenos de Linfócitos T
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Antígeno HLA-A2
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Células Th1
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Antígenos de Neoplasias
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Antígenos Virais
Limite:
Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article