76,585 research outputs found
Transcriptional regulation of MHC class II genes
No full textMHC class II molecules play a fundamental role in the homeostasis of the immune response, functioning as receptors for antigenic peptides to be presented to regulatory T cells. Both quantitative and qualitative alterations in the expression of these molecules on the cell surface dramatically affect the onset of the immune response, and may be the basis of a wide variety of disease states, such as autoimmunity, immunodeficiencies, and cancer. Most regulation of MHC class II molecule expression is under the control of transcription mechanisms which are both cell type and development specific. In the last few years classical genetics together with molecular biology have greatly contributed to the widening of our knowledge on the regulatory mechanisms operating in the control of class II gene expression. This review deals with the latest developments in this fundamental area of immunology
Analysis of the structural heterogeneity and polymorphism of human Ia antigens. Four distinct subsets of molecules are coexpressed in the Ia pool of both DR1,1 homozygous and DR3,W6 heterozygous B cell lines
No full textFunctional significance of polymorphism among MHC class II gene promoters.
No full textCited by the Following Articles in PubMed:
Dagan A. Loisel, Matthew V. Rockman, Gregory A. Wray, Jeanne Altmann, and Susan C. Alberts. Ancient polymorphism and functional variation in the primate MHC-DQA1 5′ cis-regulatory region. Proc Natl Acad Sci U S A. 2006 October 31; 103(44): 16331–16336. Published online 2006 October 19. doi: 10.1073/pnas.0607662103.
Dissection of the role of MHC class II A and E genes in autoimmune susceptibility in murine lupus models with intragenic recombination
Danqing Zhang, Keishi Fujio, Yi Jiang, Jingyuan Zhao, Norihiro Tada, Katsuko Sudo, Hiromichi Tsurui, Kazuhiro Nakamura, Kazuhiko Yamamoto, Hiroyuki Nishimura, Toshikazu Shira, and Sachiko Hirose. Proc Natl Acad Sci U S A. 2004 September 21; 101(38): 13838–13843. Published online 2004 September 10. doi: 10.1073/pnas.0405807101.
J V Taylor, L E Gordon, and H C Polk, Jr. Early decrease in surface expression of HLA-DQ predicts the development of infection in trauma patients. Clin Exp Immunol. 2000 December; 122(3): 308–311. doi: 10.1046/j.1365-2249.1999.00832.x.
Martin Baumgart, Verena Moos, Diana Schuhbauer, and Brigitte Müller. Differential expression of major histocompatibility complex class II genes on murine macrophages associated with T cell cytokine profile and protective/suppressive effects. Proc Natl Acad Sci U S A. 1998 June 9; 95(12): 6936–6940.
B Müller and A Mitchison. The importance of the back-signal from T cells into antigen-presenting cells in determining susceptibility to parasites. Philos Trans R Soc Lond B Biol Sci. 1997 September 29; 352(1359): 1327–1330.
Structure and regulation of MHC system
No full textA short review about the molecular structure of MHC class II genes and their regulation at the transcription level
Htlv-1 infection and pathogenesis: New insights from cellular and animal models
No full textSince the discovery of the human T-cell leukemia virus-1 (HTLV-1), cellular and animal models have provided invaluable contributions in the knowledge of viral infection, transmission and progression of HTLV-associated diseases. HTLV-1 is the causative agent of the aggressive adult T-cell leukemia/lymphoma and inflammatory diseases such as the HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). Cell models contribute to defining the role of HTLV proteins, as well as the mechanisms of cell-to-cell transmission of the virus. Otherwise, selected and engineered animal models are currently applied to recapitulate in vivo the HTLV-1 associated pathogenesis and to verify the effectiveness of viral therapy and host immune response. Here we review the current cell models for studying virus–host interaction, cellular restriction factors and cell pathway deregulation mediated by HTLV products. We recapitulate the most effective animal models applied to investigate the pathogenesis of HTLV-1-associated diseases such as transgenic and humanized mice, rabbit and monkey models. Finally, we summarize the studies on STLV and BLV, two closely related HTLV-1 viruses in animals. The most recent anticancer and HAM/TSP therapies are also discussed in view of the most reliable experimental models that may accelerate the translation from the experimental findings to effective therapies in infected patients
Unveiling the hidden treasury: Ciita-driven mhc class ii expression in tumor cells to dig up the relevant repertoire of tumor antigens for optimal stimulation of tumor specific cd4+ t helper cells
No full textDespite the recent enthusiasm generated by novel immunotherapeutic approaches against cancer based on immune checkpoint inhibitors, it becomes increasingly clear that single immune-based strategies are not sufficient to defeat the various forms and types of tumors. Within this frame, novel vaccination strategies that are based on optimal stimulation of the key cell governing adaptive immunity, the CD4+ T helper cell, will certainly help in constructing more efficient treatments. In this review, we will focus on this aspect, mainly describing our past and recent contributions that, starting with a rather unorthodox approach, have ended up with the proposition of a new idea for making available an unprecedented extended repertoire of tumor antigens, both in quantitative and qualitative terms, to tumor-specific CD4+ T helper cells. Our approach is based on rendering the very same tumor cells antigen presenting cells for their own tumor antigens by gene transfer of CIITA, the major transcriptional coordinator of MHC class II expression discovered in our laboratory. CIITA-driven MHC class II-expressing tumor cells optimally stimulate in vivo tumor specific MHC class II-restricted CD4 T cells generating specific and long lasting protective immunity against the tumor. We will discuss the mechanism underlying protection and elaborate not only on the applicability of this approach for novel vaccination strategies amenable to clinical setting, but also on the consequence of our discoveries on sedimented immunological dogmas that are related to antigen presentation
Reply to the Letter to the Editor: “Importance of nasal secretions in the evaluation of mucosal immunity elicited by mRNA BNT162b2 COVID-19 vaccine” by Francavilla B et al.: Lack of a strong oral mucosal immune response: rethinking the route of COVID-19 vaccine boost administration?
No full textStructural analysis of human Ia antigens reveals the existence of a fourth molecular subset distinct from DP, DQ, and DR molecules.
No full textMonoclonal antibodies specific for carcinoembryonic antigen and produced by two hybrid cell lines.
No full textAssessment of the DQB1-DQA1 complete genotype allows best prediction for IDDM
No full textOBJECTIVE--To analyze the HLA-DQ (human leukocyte antigen) genetic association with insulin-dependent diabetes mellitus (IDDM) patients of the Northeast Italian population. RESEARCH DESIGN AND METHODS--Fifty-one IDDM patients and 52 healthy control subjects were molecularly typed for DQB1 and DQA1 loci by using allele-specific oligonucleotide probes and polymerase chain reaction amplified genomic DNA. DNA enzyme immunoassay was used to assess allele specificities. RESULTS--IDDM status strongly correlated with DQB1 alleles carrying a non-aspartic acid (non-Asp) residue in position 57 of DQ beta-chain and DQA1 alleles with an arginine (Arg) residue in position 52 of DQ alpha-chain. Individuals with two DQB1 (non-Asp) alleles and two DQA1(Arg) alleles had the highest relative risk for disease: they constituted approximately 40% of IDDM patients compared with 0% of control subjects. Heterozygosis at either residue 57 of DQB1 or residue 52 of DQA1 was sufficient to abrogate statistical significance for disease association, although 47% of IDDM patients were included in these two groups compared with 21% of normal control subjects. On the other hand, the presence of two DQB1 alleles with Asp in position 57 was sufficient to confer resistance to disease irrespective of the DQA1 genotype. CONCLUSIONS--The results demonstrate that the complete HLA-DQ genotype, more than a single DQB1 or DQA1 locus, should be determined to estimate the highest risk for disease. Screening a population for preventive purposes and/or early signs of IDDM should then take advantage of this result, and "susceptible homozygous" individuals should be followed very closely and considered the first group of choice for possible new therapeutic trials
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