MHC class I-restricted CD8+ T cells are a crucial component of the host defense against mycobacterial infection in mice, but it has often proved very difficult to identify the CD8 T cell response in humans. Human group 1 CD1 molecules (CD1a, -b, -c) mediate MHC-independent presentation of mycobacteria-derived lipid and glycolipid Ags to CD8+ T cells, and their intracellular localization to the endocytic system may favor efficient monitoring of phagosome-resident mycobacteria. Here, we show that bacillus Calmette-Guérin (BCG)-immunized subjects contain a significant circulating pool of CD8+ T cells that recognize BCG-infected DCs in a CD1-dependent, but MHC-independent, manner. These CD1-restricted T cells efficiently detected live, rather than dead, BCG and produced IFN-γ, an important cytokine for protection against mycobacterial infection. These results emphasize that lipid-reactive CD8+ T cells may contribute to host defense against mycobacterial infection.

No abstract

We previously reported a mouse monoclonal antibody (MAb), termed L2, specific for Helicobacter pylori urease strongly inhibited its enzymatic activity. Here, to gain insight into how this antibody affects urease activity, the epitope that was recognized by the antibody was determined. By screening a panel of overlapping synthetic peptides covering the entire sequence of the two subunits (UreA and UreB), we identified a stretch of UreB-derived 19 amino acid (aa) residues (UB-33; aa 321 to 339, CHHLDKSIKEDVQFADSRI) that was specifically recognized by the L2 antibody. Further sequential amino acid deletion of the 19-mer peptide from either end allowed us to determine the minimal epitope as 8 amino acid residues (F8; SIKEDVQF) for L2 reactivity. This epitope appears to lie exactly on a short sequence which formed a flap over the active site of urease, suggesting that binding of the L2 antibody sterically inhibits access of urea, the substrate of urease. Finally, immunization of rabbits with either the 19-mer peptide or the 8-mer minimal epitope resulted in generation of antiurease antibodies that were capable of inhibiting the enzymatic activity. Since urease is critical for virulence of H. pylori, antigenic peptides that induce production of antibodies to inhibit its enzymatic activity may potentially be a useful tool as a vaccine for prevention and treatment of H. pylori infection.

Human skin contains the following two distinct DC subsets: (i) Langerhans cells (LCs), expressing Langerin but not DC-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN), are predominantly localized in the epidermis; and (ii) dermal DCs, expressing DC-SIGN but not Langerin, are observed mainly in the dermis. It is not known whether localization in the epidermis provides cues for LC differentiation. Here, we show that E-cadherin expressed by epidermal keratinocytes (KCs) is crucial for differentiation of LCs. Monocytes differentiated into LC-like cells in presence of IL-4, GM-CSF, and TGF-β1. However, these LC-like cells expressed not only Langerin but also DC-SIGN. Notably, co-culturing of these LC-like cells with KCs expressing E-cadherin or recombinant E-cadherin strongly decreased expression of DC-SIGN and further induced a phenotype similar to purified epidermal LCs. Moreover, pretreatment of LC-like cells with anti-E-cadherin-specific antibody completely abolished their Langerin expression, indicating the requirement of E-cadherin–E-cadherin interactions for the differentiation into Langerin+ cells. These findings suggest that E-cadherin expressed by KCs provide environmental cues that induce differentiation of LCs in the epidermis.

(Gut 1998;43:168-175)