Development of highly active and durable non-precious spinel transition metal sulfide (STMS)-based electrocatalysts plays a vital role in increasing the efficiency of hydrogen production via water electrolysis. Herein, we have...

T cell-mediated responses to protein antigen involve recognition of selected antigenic peptides bound to Major Histocompatibility Complex (MHC) molecules. Proteolytic digestion of protein antigens during antigen processing generates many peptide fragments that can potentially bind to MHC molecules. However, only few selected antigenic epitopes induce T cell responses, defined as "immunodominant". Identifying immunodominant epitopes from a given antigen has wide applications in development of peptide vaccines and therapies against infectious diseases, cancer, autoimmune diseases, and allergy. Currently available methods are not efficient in elucidating CD4+ T cell epitopes. Here, we provide a novel approach for identifying the immunodominant epitopes from protein antigens using a cell-free MHC class II antigen-processing assay. Two different novel antigens, Hemagglutinin (HA1) of the A/Vietnam/1203/2004 (H5N1) virus, and a recombinant form of Plasmodium falciparum liver-stage antigen 1 (LSA-NRC) were used to evaluate our assay. HLA-DR1 restricted epitopes from both proteins were identified by mass spectrometry and were tested for their ability to activate T cells in HLA-DR1 tg mice. We observed that the identified epitopes were indeed immunodominant as CD4+ T cells from mice immunized with the proteins proliferated and produced cytokines upon challenge with the identified epitopes at levels comparable to the whole protein. This cell-free assay provides a useful tool for identification of CD4+ T cell epitopes for specific MHC class II alleles.

The objectives of this research are to assess a shoe theft detection and prevention system. The theft of shoes can happen relatively frequently in Korean or Japanese societies because people often have to take off their shoes when entering and eating at a local restaurant or any other type of crowded building structure. A single pair of shoes can cost hundreds of dollars; hence, the theft of shoes can hurt people financially. This research adopts difference image comparison, with use of binary images, pixel rates, time, and a histogram that uses Bhattacharyya distance measurements. In addition, we assess the originality and quality of our research and evaluate it through video forensics studies. We hope that this research will become the catalyst for society to grow morally. The social climate of today's society is becoming ever more fraught, but we have to endeavor to change this by introducing more positivity. A central tenet of a healthy society is the rule of law and respect for property rights.

The paradigmatic model for the generation of peptide determinants for class II major histocompatibility complex molecules (MHC II) is that proteolytic fragmentation of antigen precedes the capture of the resulting peptides by MHC II (cut/trim first, bind later). However, circumstantial evidence exists to support an alternate model in which MHC II binding of antigenic epitope occurs prior to the proteolytic fragmentation of that antigen (bind first, cut/trim later). To distinguish between these two models, we analyzed the interaction of HLA-DR1 with two protein antigens, type II collagen and influenza hemagglutinin. Here, using a novel cell?free antigen processing system composed solely of purified soluble protein components, HLA-DR1, two cathepsins, and HLA-DM, combined with mass spectrometric identification of the bound peptides, we demonstrate for both antigens that; the protein antigens bind MHC class II prior to digestion by lysosomal proteases,the immunodominant epitope of the antigens are degraded by lysosomal proteases if not bound to MHC class II, andthe epitopes, when bound to MHCII, are protected from proteolytic degradation. These findings conclusively support the “bind first, cut/trim later” model and have important implications in understanding the sequence of events in antigen processing and the correlation between antigen structure and immunodominance.

Immunodominance is defined as restricted responsiveness of T cells to a few selected epitopes from complex antigens. We have established a reductionist cell-free antigen-processing system for MHC class II that constitutes five purified components: HLA-DR1, HLA-DM, and three cathepsins. This system successfully identified the physiologically selected epitopes from two model antigens. When applied for de novo epitope identification to LSA-NRC of malaria, or HA1-H5N1 (Avian Flu), the system selected epitopes that were confirmed to be immunodominant by their capacity to activate CD4+ T cells in HLA-DR1 positive human volunteers or transgenic mice (Hartman/Kim, et al. Nat Med 16, pp1333-1340 (2010). To evaluate our system to a mixture of the above antigens, the system identified the epitopes from both antigens. We tested the immunogenicity of epitopes and the parent proteins in HLA-DR1 transgenic mice immunized with the mixture of both HA1 and LSA-NRC in a recall T cell proliferation assay. T cells responded only to the HA1 and its immunodominant epitope, while little, if any stimulation against LSA-NRC and its dominant epitope were measured. These observations did not change even when the ratio of LSA-NRC:HA1was 2:1. These findings show a hierarchy for the selection of immunodominant epitopes of different proteins during antigen processing, which can be important in design of combination vaccines.