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Biomedical subjects

Yuzhang Wu

Publications and source records attributed to Yuzhang Wu.

25 records · Page 2Linked to original sources

Identification of HLA-A*0201-restricted cytotoxic T lymphocyte epitope from TRAG-3 antigen.

PURPOSE: Identification of tumor antigen and subsequent identification of T-cell epitope from these antigens make specific immunotherapy for malignant tumor applicable. Because TRAG-3 antigen is expressed in most melanomas and 54% of non-small cell lung carcinomas and HLA-A2.1-expressing individuals cover >50% in the population of China, we aim at identifying TRAG-3-encoded peptide presented by HLA-A2.1. EXPERIMENTAL DESIGN: In our study, a HLA-A2.1-restricted CTL epitope was identified by using the following four-step procedure: (a) computer-based epitope prediction from the amino acid sequence of TRAG-3 antigen; (b) peptide-binding assay to determine the affinity of the predicted peptide with HLA-A2.1 molecule; (c) stimulation of primary T-cell response against the predicted peptides in vitro; and (d) testing of the induced CTLs toward LB373-MEL cells expressing TRAG-3 antigen and HLA-A2.1. RESULTS: Of the four tested peptides, effectors induced by a peptide of TRAG-3 at residue position 58-66 lysed LB373-MEL cells expressing both TRAG-3 and HLA-A2.1. Our results indicate that peptide TRAG-3(58 approximately 66) (ILLRDAGLV) is a new HLA-A2.1-restricted CTL epitope capable of inducing TRAG-3 specific CTLs in vitro. CONCLUSIONS: Because TRAG-3 is a cancer/testis antigen expressed in most melanomas and half of non-small cell lung carcinomas, identification of the TRAG-3/HLA-A2.1 peptide ILLRDAGLV may facilitate peptide-based specific immunotherapy for various histological tumors.

Antigens, Neoplasm↗

Phage display particles expressing tumor-specific antigens induce preventive and therapeutic anti-tumor immunity in murine p815 model.

The efficacy of phage display particles expressing tumor antigen P1A35-43 in inducing protective and therapeutic anti-tumor immune responses were studied. A protective immune response against a lethal progressive P815 mastocytoma tumor cell challenge was established after subcutaneous injection of phage display particles. Furthermore, the vaccine suppressed growth of pre-existing tumors. Immunization with the hybrid phage particles elicited P1A(35-43) specific CTL responses and a Th1-dominated immune response with phage particle-specific secretion of IFN-gamma but not IL-4. Our results indicate that phage display particles might be a useful vaccine form for tumor-associated antigen epitopes in tumor immunotherapy.

Animals↗

[Immunocontraceptive effect of a synthetic chimeric peptide of sperm].

OBJECTIVE: To investigate the immunocontraceptive ability of a new synthetic chimeric peptide with 35 amino acid residues. METHODS: A chimeric peptide with 35 amino acid residues was synthesized based on the amino acid sequence of SP17, a protein specific to murine testis/sperm, and cyritestin. The purified product, with keyhole limpet hemocyanin (KLH), was injected subcutaneously into the pad of female and male Balh/C mice. Blood was extracted from the ophthalmic arteries of the mice to identify the corresponding proteins from organs of mice and/or rat and human being by Western blotting. The chimeric peptide was injected into other female mice that were then raised together with male mice in the same cages to observe their status of pregnancy. Freund' adjuvant or normal saline were injected into the controls. RESULTS: The purity of the new chemiric peptide was 95%. The highest specific IgG titre in mouse serum was 1:6000 and the highest titre of specific IgA in the washing of vaginal mucous membrane of female mice was 1:300. The specific antiserum from the mice immunized by the chimeric peptide and KLH could identify two proteins with the molecular weights of 22 000 and 55 000 from testes of mice, rats, and human being. Western blotting showed no band for the extracts of mouse liver, spleen, and kidney. The pregnancy rate of female immunized mice was 61.11%, significantly lower that those in the controls (P < 0.05). The average number of cubs in a litter was less in the experimental group than in the controls (P < 0.05). CONCLUSION: The new chimeric peptide with 35 amino acid residues stimulates powerfully humoral and mucous immunity in mice and obviously decreases the pregnancy rate and the number of cubs in each litter in mice.

Animals↗

Renal tubular epithelial expression of the coinhibitory molecule B7-DC (programmed death-1 ligand).

BACKGROUND: Renal tubular epithelial cells (TECs) function as antigen-presenting cells because they constitutively express MHC class II molecules and have the ability to present peptide antigen to CD4+T cells. However, the costimulatory signals provided by TECs for optimal T-cell activation have not been fully characterized. Increasing recognition of the importance of B7 dendritic cells (B7-DC) in immunoregulation raises the question of whether B7-DC is expressed on TECs and is involved in regulating TEC function. METHODS: B7-DC on cultured human and murine TECs was detected by flow cytometry in vitro. Immunohistochemistry was performed on human kidney biopsies. Coculture experiments were performed to confirm the role of TEC-related B7-DC in regulating CD4+T-cell activation. RESULTS: Data revealed that B7-DC is specifically expressed on TECs with inflammatory factor induced and diseased human kidney samples, including chronic glomerulonephritis, lupus nephritis, tubulointerstitial nephritis and renal cell carcinoma. B7-DC was a strong inhibitor of CD4+T-cell activation, as assessed by increased cytokine (interferon-gamma and interleukin-2) production and enhanced levels of T-cell activation marker CD69 in the presence of its blocking antibody. Blocking B7-DC/PD-1 enhanced antigen presentation. B7-DC is especially well expressed on TECs of diseased kidney samples and significantly down-regulates T-cell activation. CONCLUSIONS: We speculate that B7-DC might play an important role in maintaining peripheral tolerance, and in protecting the epithelium from immune-mediated tubulointerstitial injury.

Animals↗