Modulation of MHC Antigen Expression and Disease

Immunology Today, 1990

The regulation and expression of MHC The expression of mouse MHC class / genes and their products in vivo revea/s complex patterns of regulation. Different promoter elements, which are required for gen~ activation or modulation in response to various external stimuli, have now been char3ctenzed as well as the proteins that bind to rhem, As described here by 8rigitte David-Watine and colleagues, the picture that has graduah~/ emerged from these in vitro studies is of an intricate interplay of transacting factors that ultimately lead to the fine tuning of MHC class I expression in vivo. Complex patterns of MHC dass I expression Const/tut/~ ~pression The classical transplantation antigens encoded by the K0 D and L loci of the H-2 complex of the mouse are integral me~i'brane oroteins that function in the presentation of peptide antigens to T cells. The highly polymorphic MHC class I heavy chains (37-45 kDa) are non-covaientiy associated on the ceii surface with the non-polymorphic 132-microglobuhn (132-m) light chain (12 kDa) ~.2. Their expression is developmentally regulated. They are hard!y detectable until the midsomite stage of embryogenesis 3, and are expressed on most somatic cells of the adult, but with varying levels in different tissues and cell types, even within a given organ (summarized in Table 1). Expression is highest in lymphoid cells, but undetectable in brain cells, sperm cells at certain stages of differentiation, certain cell populations of the placenta 4-7 and undifferentiated embryonal carcinoma (EC) cells (which exhibit a vadety of traits ch,~_racteristic of the early embryo)'. 132-m is also expressed by virtually all adult cells but not by EC cellsL However, during embryogenesis, its synthesis follows a different time course so that regulation of H-2 and 132-m could be somewhat different 8. The H-2 class I multigene family includes other genes located in the Qa-Tla region, which code for 132-massociated molecules that are very similar to classical c!ass i antigens 9. io. In general, Qa-Tla antigens display less polymorphism and a restricted tissue distribution with the notable exception of the procaucts of genes 37 (Ref. 1 1) and Q4 (Ref. 12). Most of the other known products are

Immunology Today, 1995

Immunology today, 1991

It is becoming increasingly clear that regulation of MHC antigen expression by viruses and oncogenes, leading to either immune evasion or autoimmunity, is widespread and important in disease. At a recent meeting*, which brought together workers interested in tumour immunology, viral infection and the MHC, a number of mechanisms for the regulation of MHC antigen expression were revealed and the importance of balanced expression of MHC gene products to effective immunity was underlined.

Immunology Today, 1991

Current Topics in Microbiology and Immunology, 2005

Innate and adaptive immunity are connected via antigen processing and presentation (APP), which results in the presentation of antigenic peptides to T cells in the complex with the major histocompatibility (MHC) determinants. MHC class II (MHC II) determinants present antigens to CD 4+ T cells, which are the main regulators of the immune response. Their genes are transcribed from compact promoters that form first the MHC II enhanceosome, which contains DNA-bound activators and then the MHC II transcriptosome with the addition of the class II transactivator (CIITA). CIITA is the master regulator of MHC II transcription. It is expressed constitutively in dendritic cells (DC) and mature B cells and is inducible in most other cell types. Three isoforms of CIITA exist, depending on cell type and inducing signals. CIITA is regulated at the levels of transcription and post-translational modifications, which are still not very clear. Inappropriate immune responses are found in several diseases, which include cancer and autoimmunity. Since CIITA regulates the expression of MHC II genes, it is involved directly in the regulation of the immune response. The knowledge of CIITA will facilitate the manipulation of the immune response and might contribute to the treatment of these diseases.

The Journal of Immunology, 2003

MHC-related protein (MR)1 is an MHC class I-related molecule encoded on chromosome 1 that is highly conserved among mammals and is more closely related to classical class I molecules than are other nonclassical class I family members. In this report, we show for the first time that both mouse and human MR1 molecules can associate with the peptide-loading complex and can be detected at low levels at the surface of transfected cells. We also report the production of recombinant human MR1 molecules in insect cells using highly supplemented media and provide evidence that the MR1 H chain can assume a folded conformation and is stoichiometrically associated with ␤ 2-microglobulin, similar to class I molecules. Cumulatively, these findings demonstrate that surface expression of MR1 is possible but may be limited by a specific ligand or associated molecule.

Immunology Today, 1993

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