KD20 peptide is a lysine-aspartic acid peptide with 20 repeating units. KD20 peptide is used to stimulate CD4+ T cells in vitro and KD20 actions result in protection against abscesses induced by bacteria.
Immunologic paradigms classify bacterial polysaccharides as T cell-independent antigens. However,these models fail to explain how zwitterionic polysaccharides (Zps) confer protection against intraabdominal abscess formation in a T cell-dependent manner. Here,we demonstrate that Zps elicit a potent CD4+ T cell response in vitro that requires available major histocompatibility complex class II molecules on antigen-presenting cells. Specific chemical modifications to Zps show that: 1) the activity is specific for carbohydrate structure,and 2) the proliferative response depends upon free amino and carboxyl groups on the repeating units of these polysaccharides. Peptides synthesized to mimic the zwitterionic charge motif associated with Zps also exhibited these biologic properties. Lysine-aspartic acid (KD) peptides with more than 15 repeating units stimulated CD4+ T cells in vitro and conferred protection against abscesses induced by bacteria such as Bacteroides fragilis and Staphylococcus aureus. Evidence for the biologic importance of T cell activation by these zwitterionic polymers was provided when human CD4+ T cells stimulated with these molecules in vitro and adoptively transferred to rats in vivo conferred protection against intraabdominal abscesses induced by viable bacterial challenge. These studies demonstrate that bacterial polysaccharides with a distinct charge motif activate T cells and that this activity confers immunity to a distinct pathologic response to bacterial infection.
2- Cunto-Amesty G. et al. International Journal for Parasitology. 33(5-6):597-613 (2003)
The recent definition of tumour-specific immunity in cancer patients and the identification of tumour-associated antigens have generated renewed enthusiasm for the application of immune-based therapies for the treatment of malignancies. Recent developments in cancer vaccines have also been based on an improved understanding of the cellular interactions required to induce a specific anti-tumour immune response. Consequently,a number of cancer vaccines have entered clinical trials. Targeting broad-spectrum tumour-associated antigens has emerged as a strategy to lower the risk of tumour escape due to the loss of specific nominal antigen. Amongst the most challenging of tumour-associated antigens to which to target in active specific immunotherapy applications are carbohydrate antigens. As carbohydrates are intrinsically T-cell-independent antigens,more novel approaches are perhaps needed to drive specific-T-cell-dependent immune responses to carbohydrate antigens. In this context peptide mimetics of core structures of tumour-associated carbohydrate antigens might be developed to augment immune responses to these broad-spectrum antigens.
3- Kuno T,Nonoyama T,Hirao K,Kato K. Langmuir. 27(21):13154-8 (2011)
The catalytic effect of various sequential peptides for silica biomineralization has been studied. In peptide sequence design,lysine (K) and histidine (H) were selected as the standard amino acids and aspartic acid (D) was selected to promote the charge relay effects,such as in the enzyme active site. Therefore,homopolypeptides (K(10) and H(10)),block polypeptides (K(5)D(5) and H(5)D(5)),and alternate polypeptides [(KD)(5) and (HD)(5)] were designed,and the dehydration reaction ability of trimethylethoxysilane was investigated as a quantitative model of silica mineralization. The catalytic activity per basic residue of alternate polypeptide was the highest because of the charge relay effects at the surface of the peptide. In silica mineralization using tetraethoxysilane,spherical silica particles were obtained,and their size is related to the catalytic activities of the peptides in the model systems. From these results,the effect of the functional group combination by the peptide sequence design enables the control of the efficiency of mineralization and preparation of specific inorganic materials.
4- Vétizou M et al. Science. 350(6264):1079-1084 (2015)
Antibodies targeting CTLA-4 have been successfully used as cancer immunotherapy. We find that the antitumor effects of CTLA-4 blockade depend on distinct Bacteroides species. In mice and patients,T cell responses specific for B. thetaiotaomicron or B. fragilis were associated with the efficacy of CTLA-4 blockade. Tumors in antibiotic-treated or germ-free mice did not respond to CTLA blockade. This defect was overcome by gavage with B. fragilis,by immunization with B. fragilis polysaccharides,or by adoptive transfer of B. fragilis–specific T cells. Fecal microbial transplantation from humans to mice confirmed that treatment of melanoma patients with antibodies against CTLA-4 favored the outgrowth of B. fragilis with anticancer properties. This study reveals a key role for Bacteroidales in the immunostimulatory effects of CTLA-4 blockade.
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