Class II MHC molecules

Fremont, D.H., Hendrickson, W.A., Marrack, P, Kappler, J. 5tructures of an MHC class II molecule with covalently bound single peptides. Science 272 1001-1004,... 

Bacterial or viral proteins linking T-cell receptors and MHC molecules through simultaneous interaction with the constant domains of all MHC class II molecules and of T-cell receptor (3-chains. Hence, superantigens are polyclonal T-cell activators most likely involved in the development of autoimmune diseases. 

An unknown antigen presented by the major histocompatibility complex (MHC) class II molecules causes T cells to become autoreactive (Fig. 26-1). Once activated, T cells penetrate the... 

Romano, T.A., Ridgway, S.H., and Quaranta, V., MHC class-II molecules and immunoglobulins on peripheral blood lymphocytes of the bottlenose dolphin, Tursiops truncatus, J. Exp. Zool., 263, 96, 1992. 

Figure 9.3. Photograph of a mouse 7 days after i.v. injection of a coaguligand formulation consisting of truncated Tissue Factor mixed with a bispecific antibody directed at the MHC Class II molecules on the tumour vasculature and at truncated Tissue Factor. The mouse carried a C1300 muy tumour measuring approximately 10 x 10 mm in diameter at the time of treatment. Within hours after treatment the tumour blood flow was blocked by generalized blood coagulation in the tumour vasculature (not shown). Seven days after treatment, the necrotic tissue was almost completely removed by the host immune cells.

Helper T Lymphocytes (CD4) recognize viral or bacterial antigens together with MHC class II molecules on surface of antigen presenting cell, such as a macrophage. Interaction leads to cytokine secretion, initiating a cascade of iimnune reactions. 

Finally, in this brief overview of lymphocyte defects, mention should be made of mutations affecting major histocompatibility-complex (MHC) Class II molecules. These mutations affect a multiprotein transcription factor complex that regulates the expression of MHC Class II molecules (121). Affected patients have undetectable levels of MHC Class II antigens HLA-DP, DQ, and DR on the surface of monocytes and B cells. Lack of these antigen-presenting molecules leads to impaired immune response. Affected individuals have moderate lymphopenia with a severely reduced number of CD4+ T cells and normal or increased numbers of CD8+ T cells. Since MHC molecules in the thymic epithelium play a key role in positive and negative selection of primitive T cells, selection of competent T cells is also affected in the absence of MHC Class II antigens. 

Defects in MHC Class II molecules, while exposing affected subjects to a variety of infections, do not result in the severe immunodeficiency seen in patients with SCID. In contrast to mutations affecting MHC Class II molecules, defects in MHC Class I molecules are rare. Mutations affecting MHC Class I molecules are directed to genes on chromosome 6 at the MHC locus that code for peptide-transporter proteins (122). The function of these transporter proteins is to transport the peptide antigens so that a complex with the a chain of MHC Class I molecules and p 2-microglobulin is formed and transported to the surface of the cell. 

Hydroxychloroquine is an antimalarial agent with immunosuppressant properties. It is thought to suppress intracellular antigen processing and loading of peptides onto MHC class II molecules by increasing the pH of lysosomal and endosomal compartments, thereby decreasing T-cell activation. 

Antigen-presenting cells (APCs) are a heterogeneous population of cells with extraordinary immunostimulatory capacity. Some play an important role in the induction of the function of T helper cells and some communicate with other lymphocytes. Cytokines can render the ability to present antigens to various cell types. This results in the expression of MHC class II molecules, which are sometimes lacking on some cells such as endothelial cells. The different types of APCs include macrophages, dendritic cells, B cells and interdigitating cells. APCs are mostly derived from bone marrow and are distributed in lymphoid tissues and in the skin. These three types of major APCs are also called professional APCs. 

Presence of CD la molecules on cell surface Augmented expression of MHC class II molecules A lack or very low expression of costimulatory molecules IL-10 inhibits maturation... 

MHC class II molecules are made up of two membrane-spanning proteins each chain has a size of 30 kDa and is made up of two globular domains. These domains are called a-1, a-2, (3-1 and P-2. Each chain possesses an immunoglobulin-like region next to the cell membrane. MHC class II molecules are highly polymorphic. 

Castellino F. 1997. Antigen presentation by MHC Class II molecules Invariant chain function, protein trafficking and the molecular basis of diverse determinant capture. Hum Immunol. 54 159-169. 

The principal biological actions of type I IFNs include inhibition of viral replication, inhibition of cell proliferation, increase in the lytic potential of NK cells and the modulation of MHC molecule expression. They increase the expression of MHC class I molecules and decrease the expression of MHC class II molecules. 

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