Hybrid antibody mediated veto of cytotoxic T lymphocyte responses.

Strategies are being sought that allow the induction of specific tolerance to allogeneic transplants without affecting other immune functions. The so-called veto effect has been described as one such technology where CD8+ cells suppress responses of class I MHC-restricted T-lymphocyte precursors to antigens expressed by those CD8+ veto cells. Yet, veto inhibition will not be able to provide complete tolerance to allogeneic grafts since it only operates on cell populations that express CD8. Other types of cells prevalent in most organs express different tissue-specific antigens that are recognized by alloreactive T-cells. Therefore, complete tolerance to an allogeneic transplant can only be achieved if all cellular components within the graft acquire the immune-inhibitory function. Here, we studied whether the veto effect could be exploited for this purpose nevertheless. We produced a hybrid antibody (HAb) combining a mAb specific for a class I MHC molecule with a soluble CD8 molecule. We found that this HAb specifically and effectively transferred veto inhibition to different stimulator cell populations. Thus, we have developed a strategy that promises to selectively and completely tolerize graft-specific CTLs without affecting normal immune responses.

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Virosome-mediated delivery of protein antigens in vivo: efficient induction of class I MHC-restricted cytotoxic T lymphocyte activity

Vaccine ◽

10.1016/j.vaccine.2004.09.002 ◽

2005 ◽

Vol 23 (10) ◽

pp. 1232-1241 ◽

Cited By ~ 61

Author(s):

Laura Bungener ◽

Anke Huckriede ◽

Arjan de Mare ◽

Jacqueline de Vries-Idema ◽

Jan Wilschut ◽

...

Keyword(s):

T Lymphocyte ◽

Cytotoxic T Lymphocyte ◽

Class I ◽

Protein Antigens ◽

Class I Mhc ◽

Efficient Induction ◽

Lymphocyte Activity

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MHC class I antigen cross-presentation mediated by PapMV nanoparticles in human antigen-presenting cells is dependent on autophagy

PLoS ONE ◽

10.1371/journal.pone.0261987 ◽

2021 ◽

Vol 16 (12) ◽

pp. e0261987

Author(s):

David Possamaï ◽

Laïla-Aïcha Hanafi ◽

Angélique Bellemare-Pelletier ◽

Katia Hamelin ◽

Paméla Thébault ◽

...

Keyword(s):

Antigen Presentation ◽

T Lymphocyte ◽

Cytotoxic T Lymphocyte ◽

Antigen Presenting Cells ◽

Class I ◽

Class I Mhc ◽

Mhc I ◽

Cross Presentation ◽

Antigen Presenting ◽

Papmv Nanoparticles

Nanoparticles made of the coat protein of papaya mosaic virus (PapMV) and a single-strand RNA were previously shown to be an efficient antigen presentation system for the trigger of cellular immunity. Engineering of PapMV nano with a cytotoxic T lymphocyte epitope was previously shown activating specific T lymphocytes through a proteasome-independent major histocompatibility complex class I (MHC-I) cross-presentation. In this study, we provide new insights into the mechanism of the MHC-I cross-presentation mediated by PapMV nanoparticles. We demonstrate that PapMV nanoparticles do not require the transporter associated with antigen presentation (TAP), but rather depend on lysosome acidification and cathepsin S protease activity for presentation of the T cell epitope. We have also linked the induction of autophagy with this vacuolar MHC-I cross-presentation process. Interestingly, autophagy is induced in antigen-presenting cells after PapMV nanoparticles exposure and inhibition of autophagy reduce MHC-I cross-presentation. This study demonstrates that autophagy is associated with TAP- and proteasome-independent MHC-I cross-presentation. A deeper understanding of the autophagy-dependent MHC-I cross-presentation will be useful in designing vaccination platforms that aim to trigger an efficient cytotoxic T lymphocyte response.

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