MHC II protein

Figure 17.18 Roles of APC, MHC-II and T-helper cell. The APCs phagocytose bacteria, digest them, and transfer the resultant pepb des plus MHC-II proteins to the surface of APC. The role of this is to present the pepb de, as an antigen, to the Th cells. The binding activates Th cells which then secrete cytokines. The activated Th cells now proliferate to produce many more identical Th cells to bind more of the antigens on the APCs. The roles of the cytokines are discussed below.

Figure 17.36 The allergic response. A protein that enters the body is taken up by an ARC, digested and the peptides presented along with MHC-II protein on cell surface. This peptide binds to its complementary receptor on the Th2 cell, which produces cytokines that stimulate B-cells to proliferate and produce plasma cells that secrete IgE antibodies. The latter bind to mast cells. This is the process of sensitisation. Upon subsequent exposure to the antigenic protein, the antigens bind to the IgE antibodies on the mast cells to produce degranulation. This results in release of the factors that cause the allergic response. If degranulation is massive the response will be severe resulting in anaphylactic shock.

Left out of this discussion is an explanation for the source of the processed antigen on the antigen-presenting B cell. Immature B cells display a membrane-bound antibody, which interacts with circulating complementary antigen. Once bound to the antibody, the antigen is internalized, processed, and ultimately displayed by the MHC II protein on the cell surface of the same B cell. It is the interaction between such a B cell and the appropriate helper T cell that triggers the B cell to divide and differentiate. 

As indicated previously, the major cause of allogeneic tissue transplantation rejection is the polymorphic nature of the MHC phenotype between individuals. Polymorphism in MHC arises within the population because the genes for each of the MHC subclasses can exist in multiple different forms or alleles. For example, in humans there are at least 52 different forms of the MHC IB gene and at least 24 different forms of the MHC IA gene. It follows that individuals in a population can possess any one of the 52 different forms of MHC IB gene and any one of the 24 different forms of MHC 1A gene, so the number of different combinations for the six classes of MHC proteins is many millions. The situation is further complicated by the fact that each individual inherits and co-expresses a set of MHC I and II genes from each parent. This means that on each nucleated cell of the body there will be coexpressed paternally derived and maternally derived versions of the MHC IA, MHC IB and MHC IC molecules. The same principle will apply for coexpression upon APCs of paternal and maternal MHC II protein subclasses. 

Presentation of foreign (nonself) peptides by the MHC II protein to Th cells occurs in a similar manner to the MHC I proteins, requiring both the MHC II protein and T-cell surface proteins of the CD3 complex (see Table 35-1). The cell surface protein CD3 is involved in transmembrane signaling and initiation of cytokine (immune system messenger molecules) synthesis. Newly synthesized and recycled MHC II proteins are, like the MHC I proteins, ushered to the surface of the APC. 

The MHC II antigen complex on the cell surface of also contains two polypeptide chains, a and /3. The extracellular polypeptide of the two chains each consists of two domains, al and a2 and pi and pi. Similar to the MHC I complex, the peptide lies in a groove between the a i and a2 domains. The structure of a human MHC II protein and the CLIP peptide is shown in Figure 35-15. As noted earlier. Recognition of the MHC Il-peptide complex by... 

Superantigen target three key proteins of the adaptive immune response, namely the T cell receptor (TCR), the B cell receptor (BCR) and major histocompatibility complex class II (MHC II) proteins. All are members of the Ig superfamily, and contain domains of similar tertiary structures, although MHC II contains two non-Ig-like domains. The structure of the Ig-like domain consists of two (3-sheets, each of which comprises a series of anti-parallel (3-strands, connected by loops of varying length. Ig domain structures embody two separate functions the first is the association with antigens, with each other and with other proteins, such as Fc receptors or complement, while the second is maintenance of the structural integrity of the domain itself. 

MHC II proteins are likewise integral membrane proteins comprising an a-and a p-chain, each with two extracellular domains. The peptide is held in a groove between the membrane-distal, N-terminal (non-Ig-like) domains of the two chains. An individual can generate eight different MHC II peptide binding specificities, since there are four types of matched a- and P-chain gene pairs in the HLA-DR, HLA-DP and HLA-DQ loci, and contributions from the maternal... 

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