Progress of MICB/NKG2D signaling pathway in immune escape / 国际儿科学杂志

Natural killer group 2 member D(NKG2D) is an immune receptor expressed by NK cells that recognizes the human major histocompatibility complex class I polypetide-related chain(MIC) A/B on the cell surface.The interaction between NKG2D and MICA/B plays an important role in the immunosurveillance of viruses infection and cancers.In this article, we review the research progress of the MICB/NKG2D signaling pathway in immune escape including three parts: down-regulation of membrane-bound MICB, increase of secretory MICB, and polymorphism of MICB genes.

Expression of major histocompatibility complex class I polypeptide-related sequence B in adipose-derived stem cells from breast cancer patients and normal individuals

Context: Through the expression of different immunomodulatory molecules, mesenchymal stem cells (MSCs) play a significant role in the regulation of immune responses against tumor cells. Herein, the expression of major histocompatibility complex class I polypeptide-related sequence B (MIC B) as an immunomodulatory molecule was investigated on adipose-derived stem cells (ASCs) isolated from breast cancer patients (Stage II and III) and healthy individuals. Materials and Methods: ASCs were isolated enzymatically, and the expression of MIC B was measured using quantitative real-time polymerase chain reaction method before and after treatment with interferon γ (IFN-γ). The concentration of MIC B in the supernatant of ASCs and also sera of breast cancer and normal individuals were determined using ELISA method. Results: The expression of MIC B in normal ASCs and Stage II ASCs was higher than Stage III ASCs. However, after treatment with IFN-γ expression of MIC B in ASCs was conversely changed as cancer ASCs showed approximately 3.5 fold higher expression of MIC B compared to normal ASCs. The mRNA expression of MIC B in Stage III, Stage II, and normal ASCs showed 61 (P = 0.02), 13 (P = 0.01) and 3 (P > 0.05) fold higher expression after stimulation with IFN-γ compared to cells with no stimulation. Conclusion: Expression of MIC B and upregulation of this molecule in response to IFN-γ in cancer ASCs draw attention to the effective role of MSCs in the tumor microenvironment. However, more studies will be needed to further elucidate Natural-killer Group 2, member D (NKG2D) ligands-dependent immunomodulatory roles of ASCs in the tumor progression

Expressão de antígenos MHC classe I e de células CD4 e CD8 na polimiosite e dermatomiosite / MHC class I antigens, CD4 and CD8 expressions in polymyositis and dermatomyositis

Objetivo: Analisar as frequências de expressão dos antígenos de complexo principal de histocompatibilidade classe I (MHC-I) e células CD4 e CD8 no músculo esquelético na polimiosite (PM) e dermatomiosite (DM). Métodos: Estudo retrospectivo de 34 casos de PM, oito casos de DM e 29 controles com miopatias não inflamatórias. Resultados: Os antígenos MHC-I expressaram-se no sarcolema e/ou sarcoplasma em 79,4% dos casos de PM, 62,5% dos casos de DM e 27,6% dos controles (a expressão de CD4 foi observada em 76,5%, 75% e 13,8%, respectivamente). Quando os antígenos de MHC-I foram coexpressados com CD4, houve elevada suspeita de PM/DM (principalmente PM). Em 14,3% dos casos de PM/DM, observou-se a expressão isolada dos antígenos MHC-I, sem células inflamatórias. Conclusão: A expressão dos antígenos MHC-I e a positividade do CD4 podem aumentar a suspeita diagnóstica de PM/DM. Não foi observado infiltrado celular em 14,3% dos casos. .

Objective: To analyze the frequencies of the expression of major histocompatibility complex class I (MHC-I) antigens, and CD4 and CD8 cells in skeletal muscle in polymyositis (PM) and dermatomyositis (DM). Methods: This was a retrospective study of 34 PM cases, 8 DM cases, and 29 control patients with non-inflammatory myopathies. Results: MHC-I antigens were expressed in the sarcolemma and/or sarcoplasm in 79.4% of PM cases, 62.5% of DM cases, and 27.6% of controls (CD4 expression was observed in 76.5%, 75%, and 13.8%, respectively). There was a high suspicion of PM/DM (mainly PM) in participants in whom MHC-I antigens and CD4 were co-expressed. In 14.3% of PM/DM cases, we observed MHC-I antigens expression alone, without inflammatory cells. Conclusion: MHC-I antigens expression and CD4 positivity might add to strong diagnostic suspicion of PM/DM. No cellular infiltration was observed in approximately 14.3% of such cases. .

Relationship between Poor Immunogenicity of HLA-A2-Restricted Peptide Epitopes and Paucity of Naive CD8+ T-Cell Precursors in HLA-A2-Transgenic Mice

We examined the immunogenicity of H-2 class I-restricted and HLA-A2-restricted epitopes through peptide immunization of HLA-A2-transgenic mice that also express mouse H-2 class I molecules. All four of the tested epitopes restricted by H-2 class I robustly elicited T-cell responses, but four of seven epitopes restricted by HLA-A2 did not induce T-cell responses, showing that HLA-A2-restricted peptide epitopes tend to be poorly immunogenic in HLA-A2-transgenic mice. This finding was confirmed in HLA-A2-transgenic mice infected with a recombinant vaccinia virus expressing hepatitis C virus proteins. We examined the precursor frequency of epitope-specific naive CD8+ T cells in HLA-A2-transgenic and conventional C57BL/6 mice and found that the poor immunogenicity of HLA-A2-restricted peptide epitopes is related to the paucity of naive CD8+ T-cell precursors in HLA-A2-transgenic mice. These results provide direction for the improvement of mouse models to study epitope repertoires and the immunodominance of human T-cell responses.

Priming of Autoreactive CD8+ T Cells Is Inhibited by Immunogenic Peptides Which Are Competitive for Major Histocompatibility Complex Class I Binding

In the present study, we investigated if priming of autoreactive CD8+ T cells would be inhibited by competitive peptides for major histocompatibility complex (MHC) class I binding. We used a mouse model of vitiligo which is induced by immunization of Kb-binding tyrosinase-related protein 2 (TRP2)-180 peptide. Competitive peptides for Kb binding inhibited IFN-gamma production and proliferation of TRP2-180-specific CD8+ T cells upon ex vivo peptide restimulation, while other MHC class I-binding peptides did not. In mice, the capability of inhibition was influenced by T-cell immunogenicity of the competitive peptides. The competitive peptide with a high T-cell immunogenicity efficiently inhibited priming of TRP2-180-specific CD8+ T cells in vivo, whereas the competitive peptide with a low T-cell immunogenicity did not. Taken together, the inhibition of priming of autoreactive CD8+ T cells depends on not only competition of peptides for MHC class I binding but also competitive peptide-specific CD8+ T cells, suggesting that clonal expansion of autoreactive T cells would be affected by expansion of competitive peptide-specific T cells. This result provides new insights into the development of competitive peptides-based therapy for the treatment of autoimmune diseases.

Relationship of post-transplant MICA antibodies and chronic renal allograft function decline / 中华泌尿外科杂志

Objective To explore the relationship of post-transplant major histocompatibility complex class I chain-related gene A(MICA)antibody status and renal allograft function in clinical stable phase.Methods Fifty-seven patients accepted renal allografts followed up for at least 6 months were detected with the levels and specialties of MICA antibodies by Flow PRATM beads.Simultaneously,their serum ereatinine levels were tested as well.The impact of MICA antibody status on renal allograft function was assessed.Results Among the 57 patients,38 cases showed no HLA and MICA antibody.11 cases had HLA antibodies but not MICA antibody,8 cases had MICA antibodies and 3 cases had both MICA and HLA antibodies.There were 5 patients with MICA019 antibodies.3 patients with MICA027 antibodies,2 patients with MICA018 antibodies,while 1 patient with MICA004 and MICA017 antibodies,respectively.There were 9 patients with antibody positive score higher than 6,accounting 75%(9/12).Except age,there was no significant difference between patients with positive and negative MICA antibodies in the aspects of blood transfusion history,CDC,and cold ischemia time(P＞0.05).The average ages were(32.5±7.9)years for MICA antibodypositive patients and were(43.0±1 0.4)years for MICA antibody-negative patients(P=0.008).MICA antibody-positive patients without HLA antibody had higher serum creatinine level[(117.20±12.30)μmol/L]than MICA and HLA antibody-negative patients[(89.40±28.95)μmol/L,P＜0.05].Conclusions The measurement of MICA antibodies has prognostic value in the assessment of patients without HLA antibodies after renal transplantation.MICA antibody positive has clear association with chronic renal allograft function decline.

Differential Immunohistological Features of Inflammatory Myopathies and Dysferlinopathy

This study was performed in order to characterize the types of the infiltrating cells, and the expression profiles of major histocompatibility complex (MHC) class I and membrane attack complex (MAC) in patients with inflammatory myopathies and dysferlinopathy. Immunohistochemical stains were performed using monoclonal antibodies against several inflammatory cell types, MHC class I, and MAC in muscles from inflammatory myopathies and dysferlinopathy. There was significant difference in the types of infiltrating cells between polymyositis (PM), dermatomyositis (DM), and dysferlinopathy, including significantly high CD4+/CD8+ T cell ratio and B/T cell ratio in DM. In dysferlinopathy, CD4+ T cells were the most abundant and the proportions of infiltrating cell types were similar to those of DM. MHC class I was expressed in muscle fibers of PM and DM regardless of the presence of inflammatory infiltrates. MAC was expressed in necrotic fibers and vessels of PM and DM. One patient with early stage DM had a MAC deposits on endomysial capillaries. In dysferlinopathy, MAC deposit was also observed on the sarcolemma of nonnecrotic fibers. The analysis of inflammatory cells, MHC class I expressions and MAC deposits may help to differentiate dysferlinopathy from idiopathic inflammatory myopathy.