Natural T‐cell ligands that are created by genetic variants can be transferred between cells by extracellular vesicles

CD4 T cells play a central role as helper cells in adaptive immunity. Presentation of exogenous antigens in MHC class II by professional antigen‐presenting cells is a crucial step in induction of specific CD4 T cells in adaptive immune responses. For efficient induction of immunity against intracell...

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Bibliographic Details
Published in:European journal of immunology 2018-10, Vol.48 (10), p.1621-1631
Main Authors: Kremer, Anita N., Zonneveld, Marijke I., Kremer, Andreas E., der Meijden, Edith D., Falkenburg, J.H. Frederik, Wauben, Marca H.M., Nolte‐‘t Hoen, Esther N.M., Griffioen, Marieke
Format: Article
Language:English
Subjects:
Adaptive immunity
Antigen Presentation
Antigen-presenting cells
Antigen-Presenting Cells - immunology
Antigens
Basic
CD4 antigen
CD4-Positive T-Lymphocytes - immunology
Epitopes
Extracellular vesicles
Extracellular Vesicles - immunology
Extracellular Vesicles - metabolism
Focal Adhesion Kinase 2 - genetics
Focal Adhesion Kinase 2 - immunology
Genetic diversity
Genetic variance
Genetic Variation
HeLa Cells
Helper cells
Histocompatibility antigen HLA
Histocompatibility Antigens Class II - genetics
Humans
Ligands
Lymphocytes
Lymphocytes T
Major histocompatibility complex
Minor Histocompatibility Antigens - genetics
Minor Histocompatibility Antigens - immunology
Neoplasms - immunology
Phosphotransferases (Alcohol Group Acceptor) - genetics
Phosphotransferases (Alcohol Group Acceptor) - immunology
T cells
T-Lymphocytes, Helper-Inducer - immunology
Transformed cells
Tumor Immunity
Vesicles
Viruses
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Summary:CD4 T cells play a central role as helper cells in adaptive immunity. Presentation of exogenous antigens in MHC class II by professional antigen‐presenting cells is a crucial step in induction of specific CD4 T cells in adaptive immune responses. For efficient induction of immunity against intracellular threats such as viruses or malignant transformations, antigens from HLA class II‐negative infected or transformed cells need to be transferred to surrounding antigen‐presenting cells to allow efficient priming of naive CD4 T cells. Here we show indirect antigen presentation for a subset of natural HLA class II ligands that are created by genetic variants and demonstrated that (neo)antigens can be transferred between cells by extracellular vesicles. Intercellular transfer by extracellular vesicles was not dependent on the T‐cell epitope, but rather on characteristics of the full‐length protein. This mechanism of (neo)antigen transfer from HLA class II‐negative cells to surrounding antigen‐presenting cells may play a crucial role in induction of anti‐tumor immunity. For efficient priming of CD4 T cells in tumor immunity, (neo)antigens need to be transferred from HLA class II‐negative tumor cells to surrounding antigen‐presenting cells. We showed indirect antigen presentation for a subset of natural HLA class II ligands and demonstrated that (neo)antigens can be transferred between cells by extracellular vesicles.
ISSN:0014-2980
1521-4141
DOI:10.1002/eji.201747152