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10.4049/jimmunol.1202489

http://scihub22266oqcxt.onion/10.4049/jimmunol.1202489
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C4471340!4471340!23729440
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suck abstract from ncbi


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pmid23729440      J+Immunol 2013 ; 191 (1): 60-9
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  • Human Plasmacytoid Dendritic Cells Efficiently Capture HIV-1 Envelope Glycoproteins via CD4 for Antigen Presentation #MMPMID23729440
  • Sandgren KJ; Smed-Sörensen A; Forsell MN; Soldemo M; Adams WC; Liang F; Perbeck L; Koup RA; Wyatt RT; Hedestam GBK; Loré K
  • J Immunol 2013[Jul]; 191 (1): 60-9 PMID23729440show ga
  • Advances in HIV-1 vaccine clinical trials and preclinical research indicate that the virus envelope glycoproteins (Env) are likely to be an essential component of a prophylactic vaccine. Efficient antigen uptake and presentation by dendritic cells (DCs) is important for strong CD4+ T helper cell responses and the development of effective humoral immune responses. Here, we examined the capacity of distinct primary human DC subsets to internalise and present recombinant Env to CD4+ T cells. Consistent with their specific receptor expression, skin DCs bound and internalised Env via C-type lectin receptors (CLRs) while blood DC subsets, including CD1c+ myeloid DCs (MDCs), CD123+ plasmacytoid DCs (PDCs) and CD141+ DCs exhibited a restricted repertoire of CLRs and relied on CD4 for uptake of Env. Despite a generally poor capacity for antigen uptake compared to MDCs, the high expression of CD4 on PDCs allowed them to bind and internalise Env very efficiently. CD4-mediated uptake delivered Env to EEA1+ endosomes that progressed to Lamp1+ and MHC class II+ lysosomes where internalised Env was degraded rapidly. Finally, all three blood DC subsets were able to internalise an Env-CMV pp65 fusion protein via CD4 and stimulate pp65-specific CD4+ T cells. Thus, in the in vitro systems described here, CD4-mediated uptake of Env is a functional pathway leading to antigen presentation and this may therefore be a mechanism utilised by blood DCs, including PDCs, for generating immune responses to Env-based vaccines.
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