Class II MHC proteins

Murthy, V.L., 5tern, L.J. The class II MHC protein HLA-Drl in complex with an endogenous peptide implications for the structural basis of the specificity of peptide binding. Structure 5 1385-1396, 1997. 

Class II MHC proteins also consist of two peptide chains, which are related to each other. MHC 11 molecules are found on all anti-gen-presenting cells in the immune system. They serve for interaction between these cells and CD4-carrying T helper cells. 

These proteins consist of a and /3 chains, (a) In class I MHC proteins, the small /3 chain is invariant but the amino acid sequence of the a chain exhibits a high degree of variability, localized in specific domains of the protein that appear on the outside of the cell. Each human produces up to six different a chains for class I MHC proteins, (b) In class II MHC proteins, both the a and /3 chains have regions of relatively high variability near their amino-terminal ends. 

Class II MHC proteins occur on the surfaces of a few types of specialized cells, including macrophages and B lymphocytes that take up foreign antigens. Like class I MHC proteins, the class II proteins are highly polymorphic, with many variants in the human popula-... 

The two classes of MHC proteins are displayed on different cell types. Class I MHC proteins are found on almost all nucleated cells, including killer T cells. Class II MHC proteins are found mainly on cells involved in the immune response, including antigen-presenting cells, B cells, and T helper cells, but not T killer cells. 

Class II MHC proteins present peptides to a class of lymphocytes known as helper lymphocytes, which stimulate antibody production against the peptides. In this case, the MHC associated peptides are derived by intracellular degradation of extracellular antigens imported into the cell. Association of a peptide foreign to... 

Helper T Cells Stimulate Cells That Display Foreign Peptides Bound to Class II MHC Proteins... 

Figure 33.32. Presentation of Peptides from Internalized Proteins. Antigen-presenting cells bind and internalize foreign proteins and display peptides that are formed from the digestion of these proteins in Class II MHC proteins.

Figure 33.33. Class II MHC Protein. A class IIMHC protein consists of homologous a and P chains, each of which has an amino-terminal domain that constitutes half of the peptide-binding structure, as well as a carboxyl-terminal immunoglobulin domain. The peptide-binding site is similar to that in class I MHC proteins except that it is open at both ends, allowing class II MHC proteins to bind longer peptides than those bound by class I.

Figure 33.35. Variations on a Theme. (A) Cytotoxic T cells recognize foreign peptides presented in class I MHC proteins with the aid of the coreceptor CDS. (B) Helper T cells recognize peptides presented in class II MHC proteins by specialized antigen-presenting cells with the aid of the coreceptor CD4.

Stern LJ, Brown JH, Jardetzky TS, Gorga JC, Urban RG. Strominger JL, Wiley DC (1994) Crystal structure of the human class II MHC protein HLA-DR I complexed with an influenza virus peptide. Nature 368 215-221. 

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