The role of tetraspanin CD63 in antigen presentation via MHC class II

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The role of tetraspanin CD63 in antigen presentation via MHC class II. / Petersen, SH; Odintsova, Elena; Haigh, Tracey; Rickinson, Alan; Taylor, Graham; Berditchevski, Fedor.

In: European Journal of Immunology, Vol. 41, No. 9, 01.09.2011, p. 2556-2561.

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@article{d468257a90af40899951e113556e08c0,
title = "The role of tetraspanin CD63 in antigen presentation via MHC class II",
abstract = "Interactions between MHC class II (MHC II)-positive APCs and CD4(+) T cells are central to adaptive immune responses. Using an Epstein-Barr virus (EBV)-transformed B lymphoblastoid cell line (LCL) as MHC II-positive APCs and CD4(+) T-cell clones specific for two endogenously expressed EBV antigens, we found that shRNA knockdown of the tetraspanin protein CD63 in LCL cells consistently led to increased CD4(+) T-cell recognition. This effect was not due to enhanced antigen processing nor to changes in MHC II expression since CD63 knockdown did not influence the amount or dimerization of MHC II in LCL cells. We therefore investigated the possible involvement of exosomes, small MHC II- and tetraspanin-abundant vesicles which are secreted by LCL cells and which we found could themselves activate the CD4(+) T-cell clones in an MHC II-dependent manner. While equal loadings of exosomes purified from the control and CD63(low) LCLs stimulated T cells to a comparable degree, we found that exosome production significantly increased following CD63-knockdown, suggesting that this may underlie the greater T-cell stimulatory capacity of the CD63(low) LCLs. Taken together, our data reveal a new insight into the mechanisms by which tetraspanins are involved in the regulation of MHC II-dependent T-cell stimulation.",
keywords = "T cell, CD4, CD63, Antigen presentation, MHC class II",
author = "SH Petersen and Elena Odintsova and Tracey Haigh and Alan Rickinson and Graham Taylor and Fedor Berditchevski",
year = "2011",
month = sep,
day = "1",
doi = "10.1002/eji.201141438",
language = "English",
volume = "41",
pages = "2556--2561",
journal = "European Journal of Immunology",
issn = "0014-2980",
publisher = "Wiley-VCH Verlag",
number = "9",

}

RIS

TY - JOUR

T1 - The role of tetraspanin CD63 in antigen presentation via MHC class II

AU - Petersen, SH

AU - Odintsova, Elena

AU - Haigh, Tracey

AU - Rickinson, Alan

AU - Taylor, Graham

AU - Berditchevski, Fedor

PY - 2011/9/1

Y1 - 2011/9/1

N2 - Interactions between MHC class II (MHC II)-positive APCs and CD4(+) T cells are central to adaptive immune responses. Using an Epstein-Barr virus (EBV)-transformed B lymphoblastoid cell line (LCL) as MHC II-positive APCs and CD4(+) T-cell clones specific for two endogenously expressed EBV antigens, we found that shRNA knockdown of the tetraspanin protein CD63 in LCL cells consistently led to increased CD4(+) T-cell recognition. This effect was not due to enhanced antigen processing nor to changes in MHC II expression since CD63 knockdown did not influence the amount or dimerization of MHC II in LCL cells. We therefore investigated the possible involvement of exosomes, small MHC II- and tetraspanin-abundant vesicles which are secreted by LCL cells and which we found could themselves activate the CD4(+) T-cell clones in an MHC II-dependent manner. While equal loadings of exosomes purified from the control and CD63(low) LCLs stimulated T cells to a comparable degree, we found that exosome production significantly increased following CD63-knockdown, suggesting that this may underlie the greater T-cell stimulatory capacity of the CD63(low) LCLs. Taken together, our data reveal a new insight into the mechanisms by which tetraspanins are involved in the regulation of MHC II-dependent T-cell stimulation.

AB - Interactions between MHC class II (MHC II)-positive APCs and CD4(+) T cells are central to adaptive immune responses. Using an Epstein-Barr virus (EBV)-transformed B lymphoblastoid cell line (LCL) as MHC II-positive APCs and CD4(+) T-cell clones specific for two endogenously expressed EBV antigens, we found that shRNA knockdown of the tetraspanin protein CD63 in LCL cells consistently led to increased CD4(+) T-cell recognition. This effect was not due to enhanced antigen processing nor to changes in MHC II expression since CD63 knockdown did not influence the amount or dimerization of MHC II in LCL cells. We therefore investigated the possible involvement of exosomes, small MHC II- and tetraspanin-abundant vesicles which are secreted by LCL cells and which we found could themselves activate the CD4(+) T-cell clones in an MHC II-dependent manner. While equal loadings of exosomes purified from the control and CD63(low) LCLs stimulated T cells to a comparable degree, we found that exosome production significantly increased following CD63-knockdown, suggesting that this may underlie the greater T-cell stimulatory capacity of the CD63(low) LCLs. Taken together, our data reveal a new insight into the mechanisms by which tetraspanins are involved in the regulation of MHC II-dependent T-cell stimulation.

KW - T cell

KW - CD4

KW - CD63

KW - Antigen presentation

KW - MHC class II

U2 - 10.1002/eji.201141438

DO - 10.1002/eji.201141438

M3 - Article

C2 - 21660937

VL - 41

SP - 2556

EP - 2561

JO - European Journal of Immunology

JF - European Journal of Immunology

SN - 0014-2980

IS - 9

ER -