Is microbial infection always harmful? / 中华实验眼科杂志

It is possible for microbial infection (including parasitic infection) to disrupt the balance of autoimmune tolerance,result in the dysfunction of immune system,and make the organism encountered with the attack of the autoimmune disease.As one of the common places between foreign antigens and autoantigens,molecular mimicry is believed to play a vital role in the pathogenesis of autoimmune diseases.However,a large number of studies suggest that rather than inducing various symptoms of autoimmune diseases,many infection of microorganisms covered with mimic peptide of the autoantigen may even protect the infected organism from the disease at the level of antibodies or T cells when the analogous antigen invaded again.The present paper reviews the possible prognosis after microbial infection based on molecular mimicry.

Heat shock protein 110 improves the immunological effect of an altered peptide ligand of human papilloma virus type 16 E711-20 peptide / 中华皮肤科杂志

ObjectiveTo investigate the adjuvant effect of heatshock protein 110(HSP110) on the immune responses induced by an altered peptide ligand of human papilloma virus type 16 E711-20 peptide (HPV16E711-20).Methods The complex of HSP110 and an altered peptide ligand of HPV16E711-20 was constructed in vitro.Fifteen 6-week-old C57BL/6 female mice were randonly and equally divided into 3 groups,including complex group,ligand group,and phosphate buffered solution (PBS) group,to receive intraperitoneal immunization with the complex (100 μg),peptide (10 μg),and PBS (100 μl) respectively.Immunization was carried out with an interval of 2 weeks for 2 times.Two weeks after the last immunization,the mice were sacrificed followed by the isolation of splenocytes.MTT assay was performed to evaluate the proliferation activity of splenocytes,intracellular staining for interferon(INF)-γ to detect cytotoxic T lymphocytes (CTLs),standard chromium-51 (51Cr) release assay to estimate the lethal effect of specific CTLs on target cells.Statistical analysis was performed by using t test with SPSS 10.0 software.Differences were considered as statistically significant when the P value was less than 0.05.ResultsA significant increase was observed in the proliferation index ( 1.87 ± 0.122 vs.0.32 ± 0.071,t =4.01,P ＜ 0.01 ) of,and percentage of CD8+IFN-γ+ T lymphocytes(3.9％ vs.0.4％,t =3.88,P ＜ 0.01 ) among splenocytes from the complex group compared with the ligand group.At the effector-to-target ratio of 100 ∶ 1,50 ∶ 1,25∶ 1 and 12.5 ∶ 1,the death rate of target cells was 54.7％,72.2％,61.5％ and 39.8％ respectively after incubation with CTLs from the compleximmunized mice,higher than that from the ligand-immunized mice (35.2％,49.3％,28.1％,17.4％,respectively).ConclusionHSP110 could enhance the immunological effect of the altered peptide ligand of HPV16E711-20,and can serve as an immunological adjuvant.

Inhibitory effect of HLA-DR1-specific influenza virus hemagglutitin peptide on T cell activation / 中华风湿病学杂志

Objective To evaluate the impact of influenza virus hemagglutitin (HA) 306-318 peptide on T cell activation and to investigate the inhibitory effect of the altered HA306-318 peptide on T cell proliferation. Methods HA306-318 peptide and its mutant containing amino acid substitutions were synthesized. They were used in T cell activation assay using HLA-DR1 transfected cells. Responses were determined by MTT proliferation assays. The HA mutant without stimulating effect on T cells was then examined by inhibiting HLA-DR1-restricted T cell activation. Results It was demonstrated in this study that the altered HA306-318 peptide bound to HLA-DR1 molecule on L57.23 cells transfected with HLA-DR1 cDNA, but not on the control cells. The altered HA306-318 peptide had no stimulating effect on T cells compared with the wild type HA306-318 which induced T cell proliferation. It was shown that the altered HA peptide inhibited T cell activation mediated by wild type HA306-318 as well as by CⅡ263-272 which was the specific T cell antigen. Conclusions This study suggests that HA306-318 peptide is antigenic and can induce responses in HLA-DR1 specific T cells. Altered HA306-318 peptide is hyporesponsive in T cell activation with inhibitory effect on antigen-driven T cell responses, and it is potentially a therapeutic agent in rheumatoid arthritis.

Mucosal administration of altered CⅡ263-272 peptide inhibits collagen-induced arthritis / 北京大学学报(医学版)

Objective:To evaluate the effect of mucosal administration of altered collagen Ⅱ(CⅡ)263-272 peptide(267Q→A,270K→A and 271G→A) on collagen induced arthritis(CIA),and to explore the mechanism of the inhibitory effect of the altered CⅡ263-272 peptide on CIA.Methods:CIA was induced in Lewis rats by immunization with bovine CⅡ.Altered CⅡ263-272 peptide was given intranasally beginning from the onset of arthritis(100 ?g/dose,daily for 5 doses and continuing every other day for other 7 doses).Wild CⅡ263-272 peptide(100 ?g/dose) or PBS was administered as controls with the same procedure.Therapeutic effects were evaluated by arthritis scores,body weight change,and joint pathologic scores.The anti-CⅡ antibody and its subtypes were measured with ELISA.The cytokines of IFN-? and IL-10 were measured with ELISA.The induction of regulatory T cells was assessed by FACS analysis of percentage of peripheral CD4+CD25+ T cells,and by real-time PCR analysis of the expression of Foxp3 and TGF-? mRNA.Results:(1) Following treatment with the altered CⅡ263-272 peptide,arthiritis scores were reduced and body weight was increased.The mean arthritis scores of rats treated with altered peptide,wild peptide and PBS were 2.50?2.43,4.50?2.23 and 6.33?2.73,respectively.The altered peptide could retard the histologic lesion of the joints.(2) The titers of anti-CⅡ antibodies IgG and IgG1 in the three groups were similar,but the IgG2a in altered peptide-treated rats decreased markedly as compared with PBS-treated rats(0.56?0.19 vs 0.95?0.29,P

HLA-DRB1 binding CⅡ263-272 peptide inhibits collagen-induced arthritis / 中国免疫学杂志

Objective:To study the inhibition of collagen-induced arthritis by an altered CⅡ263-272 peptide(sub268-270) with three consecutive substitutions of TCR-contacting residues.Methods:Arthritis was induced by bovine collagen type Ⅱ. The altered peptide sub268-270 was given intravenously with a dose of 90 ?g once a week. Peptide control and blank control were treated with similar approaches. The therapeutic effect of the altered peptide was evaluated by arthritis score index, radiological score and pathological score.Results:The arthritis score of rats treated with altered peptide, control peptide and blank control were 5.60?1.24, 11.20?1.21 and 11.80?1.22 respectively(P

Modification and identification of tyrosinase related protein-2(180-188) epitope / 第三军医大学学报

Objective To modify HLA-A2.1 restricted epitope of tyrosinase related protein-2 (TRP-2) (180-188) of human melanoma differentiation antigen and enhance HLA-A2.1 molecule its affinity to. Methods The TRP-2 (180-188) nave epitope was altered with the predominant amino acid for the primary anchor residues and auxiliary anchor residues. Altered peptide ligands (APLs) were scanned by polynomial method, the quantitative motif method and OSAR methods. The analogues their affinity to HLA-A2.1 molecule were assayed. Results Compared with the nave peptide, APLs had stronger affinity to HLA-A2 molecules. Conclusion Our results suggest that altered nave epitope with P1 (Y) and/or P2(L, M) can enhance affinity to HLA-A2 molecule. However, the immunogical efficacy of APLs needs to be identified in studies in vitro and in vivo.