MHC class II
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Schematic representation of MHC class II MHC (major histocompatibility complex) Class II molecules are found only on a few specialized cell types, including macrophages, dendritic cells and B cells, all of which are professional antigen-presenting cells (APCs). The peptides presented by class II molecules are derived from extracellular proteins (not cytosolic as in class I); hence, the MHC class II-dependent pathway of antigen presentation is called the endocytic or exogenous pathway. Loading of class II molecules must still occur inside the cell; extracellular proteins are endocytosed, digested in lysosomes, and bound by the class II MHC molecule prior to the molecule's migration to the plasma membrane.
Contents
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1 Structure
2 Reaction to bacteria 3 Synthesis 4 Genes 5 References 6 See also 7 External links
[edit] Structure
Like MHC class I molecules, class II molecules are also heterodimers, but in this case consist of two homologous peptides, an and chain, both of which are encoded in the MHC. [1] Because the antigen-binding groove of MHC class II molecules is open at both ends while the corresponding groove on class I molecules is closed at each end, the antigens presented by MHC class II molecules are longer, generally between 15 and 24 amino acid residues long.
[edit] Reaction to bacteria
Because class II MHC is loaded with extracellular proteins, it is mainly concerned with presentation of extracellular pathogens (for example, bacteria that might be infecting a wound or the blood). Class II molecules interact exclusively with CD4+ ("helper") T cells (TH2). The helper T cells then help to trigger an appropriate immune response which may include localized inflammation and swelling due to recruitment of phagocytes or may lead to a full-force antibody immune response due to activation of B cells.
[edit] Synthesis
During synthesis of class II MHC in the endoplasmic reticulum, the and chains are produced and complexed with a special polypeptide known as the invariant chain. The nascent MHC class II protein in the rough ER has its peptide-binding cleft blocked by the invariant chain (Ii; a trimer) to prevent it from binding cellular peptides or peptides from the endogenous pathway (such as those that would be loaded onto class I MHC). The invariant chain also facilitates the export of class II MHC from the ER to the golgi, followed by fusion with a late endosome containing endocytosed, degraded proteins. The invariant chain is then broken down in stages by proteases called cathepsins, leaving only a small fragment known as CLIP which maintains blockage of the peptide binding cleft on the MHC molecule. An MHC class II-like structure, HLA-DM, facilitates CLIP removal and allows the binding of peptides with higher affinities. The stable class II MHC is then presented on the cell surface.
Genes
Alpha Beta HLA-DM HLA-DMA HLA-DMB HLA-DO HLA-DOA HLA-DOB HLA-DP HLA-DPA1 HLA-DPB1 HLA-DQ HLA-DQA1, HLA-DQA2 HLA-DQB1, HLA-DQB2 HLA-DRB1, HLA-DRB3, HLA-DRB4, HLAHLA-DR HLA-DRA DRB5
