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10.4049/jimmunol.1501476

http://scihub22266oqcxt.onion/10.4049/jimmunol.1501476
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C4779666!4779666!26856698
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suck abstract from ncbi


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pmid26856698      J+Immunol 2016 ; 196 (6): 2457-65
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  • LAMP-2C inhibits MHC class II presentation of cytoplasmic antigens by disrupting chaperone-mediated autophagy #MMPMID26856698
  • Pérez L; McLetchie S; Gardiner GJ; Deffit SN; Zhou D; Blum JS
  • J Immunol 2016[Mar]; 196 (6): 2457-65 PMID26856698show ga
  • Cells utilize multiple autophagy pathways to sequester macromolecules, senescent organelles, and pathogens. Several conserved isoforms of the lysosome-associated membrane protein (LAMP)-2 regulate these pathways influencing immune recognition and responses. LAMP-2A is required for chaperone-mediated autophagy (CMA) which promotes Ag capture and MHC class II (MHCII) presentation in B cells and signaling in T cells. LAMP-2B regulates lysosome maturation to impact macroautophagy (MA) and phagocytosis. Yet, far less is known about LAMP-2C function. While LAMP2A and LAMP2B mRNA were broadly detected in human tissues, LAMP2C expression was more limited. Transcripts for the three LAMP2 isoforms increased with B cell activation, although specific gene induction varied depending on TLR versus BCR engagement. To examine LAMP-2C function in human B cells and specifically its role in Ag presentation, ectopic gene expression was used. Increased LAMP-2C expression in B cells did not alter MHCII expression or invariant chain processing, but did perturb cytoplasmic Ag presentation via CMA. MHCII presentation of epitopes from exogenous and membrane Ags was not affected by LAMP-2C expression in B cells. Similarly, changes in B cell LAMP-2C expression did not impact MA. The gene expression of other LAMP2 isoforms as well as the proteasome and lysosomal proteases activities were unperturbed by LAMP-2C ectopic expression. LAMP-2C levels modulated the steady-state expression of several cytoplasmic proteins which are targeted for degradation by CMA and diminished peptide translocation via this pathway. Thus, LAMP-2C serves as a natural inhibitor of CMA which can selectively skew MHCII presentation of cytoplasmic Ags.
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