Heparan sulfates targeting increases MHC class I- and MHC class II-restricted antigen presentation and CD8⁺ T-cell response

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• 作者：Delphine Knittel^a ; Adeline Gadzinski^a ; Sté ; phane Hua^a ; Jordan Denizeau^b ; ^c ; ^d ; Alexandra Savatier^a ; Philippe de la Roch&egrave ; re^b ; ^c ; ^d ; Jean-Claude Boulain^a ; Sebastian Amigorena^b ; ^c ; ^d ; Eliane Piaggio^b ; ^c ; ^d ; Christine Sedlik^b ; ^c ; ^d ; Michel Lé ; onetti^a ; ^{michel.leonetti@cea.fr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Tat ; transcriptional transactivator ; DT ; diphtheria toxin ; DC ; dendritic cell ; HSPG ; heparan sulfate proteoglycan
• 刊名：Vaccine
• 出版年：2016
• 出版时间：8 June 2016
• 年：2016
• 卷：34
• 期：27
• 页码：3093-3101
• 全文大小：1104 K

文摘

Heparan sulfates (HS) are carbohydrate moieties of HS proteoglycans (HSPGs). They often represent alternative attachment points for proteins or microorganisms targeting receptors. HSPGs, which are ubiquitously expressed, thereby participate in numerous biological processes. We previously showed that MHC class II-restricted antigen presentation is increased when antigens are coupled to HS ligands, suggesting that HSPGs might contribute to adaptive immune responses. Here, we examined if HSPG targeting influences other aspects of immune responses. We found that coupling of an HS ligand to the antigen increases antigen presentation to CD4⁺ and CD8⁺ T-cells after antigen targeting to membrane immunoglobulins or to MHC-II molecules. Moreover, this increased stimulating capacity correlates with an enhanced CD8⁺ immune response in mice. Last, animals control more effectively the growth of Ova-expressing tumour cells when they are immunized with an Ova construct targeting HSPGs and MHC-II molecules. Our results indicate that ubiquitous molecules can influence both MHC class I- and MHC class II-restricted antigen presentation and behave as co-receptors during T-cell stimulation. Moreover, they suggest that tumour-antigens endowed with the ability to target both HSPGs and MHC-II molecules could be of value to increase CD8⁺ immune response and control tumour-growth, opening new perspectives for the design of highly immunogenic protein-based vaccines.