Study On Characterization And Function Of Chicken Heat Shock Protein 108

Heat shock proteins (HSPs) or stress-induced proteins are expressed in all living cells and among the most abundant proteins in living cells. They are expressed at high levels constitutively; however, the expression of some members of the HSP family is induced by stress-causing conditions such as heat shock, glucose deprivation, etc. HSPs are the most conserved protein we have known, and there are highly homologous in one family. Glycoprotein 96 is the endoplasmic reticulum (ER) resident member of heat shock protein family. Recently, it has been observed that gp96, when purified from cells, are associated with a broad range of peptides derived from that particular cell, such that the HSPs chaperone the antigenic repertoire of the cells from which they are purified. Then, gp96-antigenic peptides complex pass the peptides to macrophage or other APC in a receptor-mediated mechanism, at last peptides were presented to MHC I molecules and activated CTL and memory cells, elicited immune response to tumor or virus from which they are isolated. Generally considered, gp96 are not antigenic per se, but act as earners of antigenic peptides.Dr. Meng Songdong, from Institute of Microbiology, Chinese Academy of Sciences, was first isolated an antigenic peptide of HBV from gp96, which was from the tumor liver tissues induced by HBV infection. After amino acid sequencing analysis, it was confirmed that the peptide was from HBV core antigen. This progress was published on the famous journal of Lancet (2001). Complexes of heat shock protein and peptides have been investigated for use as tumor vaccines. This finding suggested a possible association of the isolated HBV-specific peptide with gp96 in vivo. The potential of this gp96-peptide complex as a therapeutic vaccine for HBV-induced hepatocellular carcinoma should be investigated. A similar approach should also be taken for other virus-induced tumors.Marek's disease virus (MDV) is an alpha-herpesvirus binding with cells, which can induce lymphomatous disease of chickens. It brings a lot of damages to chicken farming.On the other hand, there is more widely biological meaning in comparative medicine to study on MDV deeply. MDV is the first vaccine broadly used to prevent tumor disease induced by virus. It is also an ideal model for studying on virus tumors, especially herpesvirus tumors. The progresses of mammalian gp96 provide a good way to study MDV. Chicken hsp108 is the homolog of mammalian gp96, but the research on hsp108 is focus on the function as a transferrin binding protein all along. So. there is important meaning studying deeply on chicken hsp108.In this experiment, hsp108 genes from normal chickens liver tissues of different breeds were obtained by RT-PCR, and their amino acid sequences were induced by nucleotides; Also, hsp108 genes from tumor liver tissues of SPF chicken and Chinese hepatoma cell line were obtained by the same method. Polymorphism analysis were carried out using soft wares. It appeared that no amino acid difference between hsp108 genes from normal chickens liver tissues of different breeds, though some nucleotides changes were found; There was one amino acid difference between chicken hsp108 from liver and oviduct (published sequence), it shows that differences may be existent among different organs; In addition, there was only one nucleotide variation between hsp108 genes from normal tissue and tumor tissue, but no amino acid difference was found, but two amino acids of Chinese hepatoma cell line were mutated compared with normal human gp96 (published sequence), it seems that under the condition of cancers or infectious diseases, there exists a trend of gp96 variation.Gp96 has been proved to be immunogenic to cancers and infectious diseases. In recent years, the deep research to mammalian gp96 on immune mechanism and advantage as a vaccine supplies a new way for precaution tumor and infectious diseases. The progresses of mammalian gp96 provide a good way to study MDV. Chicken hsp108 is the homolog of mammalian gp96, but the research...