| First Author | Porter GW | Year | 2011 |
| Journal | J Immunol | Volume | 187 |
| Issue | 8 | Pages | 4151-60 |
| PubMed ID | 21918198 | Mgi Jnum | J:179303 |
| Mgi Id | MGI:5301762 | Doi | 10.4049/jimmunol.1003137 |
| Citation | Porter GW, et al. (2011) TLR agonists downregulate H2-O in CD8alpha- dendritic cells. J Immunol 187(8):4151-60 |
| abstractText | Peptide loading of MHC class II (MHCII) molecules is catalyzed by the nonclassical MHCII-related molecule H2-M. H2-O, another MHCII-like molecule, associates with H2-M and modulates H2-M function. The MHCII presentation pathway is tightly regulated in dendritic cells (DCs), yet how the key modulators of MHCII presentation, H2-M and H2-O, are affected in different DC subsets in response to maturation is unknown. In this study, we show that H2-O is markedly downregulated in vivo in mouse CD8alpha(-) DCs in response to a broad array of TLR agonists. In contrast, CD8alpha(+) DCs only modestly downregulated H2-O in response to TLR agonists. H2-M levels were slightly downmodulated in both CD8alpha(-) and CD8alpha(+) DCs. As a consequence, H2-M/H2-O ratios significantly increased for CD8alpha(-) but not for CD8alpha(+) DCs. The TLR-mediated downregulation was DC specific, as B cells did not show significant H2-O and H2-M downregulation. TLR4 signaling was required to mediate DC H2-O downregulation in response to LPS. Finally, our studies showed that the mechanism of H2-O downregulation was likely due to direct protein degradation of H2-O as well as downregulation of H2-O mRNA levels. The differential H2-O and H2-M modulation after DC maturation supports the proposed roles of CD8alpha(-) DCs in initiating CD4-restricted immune responses by optimal MHCII presentation and of CD8alpha(+) DCs in promoting immune tolerance via presentation of low levels of MHCII-peptide. |
