Overall, despite the limitations as the result of serology and the possibility of natural selection acting on this system, the analysis of the GM polymorphism has been very useful in revealing the effects of both geographic and cultural differentiations on the genetic structure of modern human populations, and has provided noteworthy examples of the usefulness of this immunogenetic complex for

anthropology. The HLA molecules are peptide-binding molecules encoded by genes in the HLA complex on chromosome 6 (see ref. 37 for a review). They are divided into two classes, class I and class II, which both present peptide fragments of antigens to T cells. Some class I molecules also interact with natural killer (NK) cells. The HLA class I molecules consist of a polymorphic α heavy chain that is non-covalently Stem Cell Compound Library manufacturer bound to a small non-polymorphic β chain (β2m, encoded by a gene on chromosome 15). The α chain includes three extracellular domains, two of which (α1 and α2) form a peptide-binding cleft. The classical HLA class I molecules encompass the A, B and C series of molecules, encoded by three different corresponding α chain loci. They are extremely polymorphic (see next section) and expressed in almost all nucleated cells. They bind short peptide fragments (8–10 amino acids long) derived selleckchem primarily from endogenous proteins and present them at the cell membrane.

Here CD8+ T cells with appropriate T-cell receptors will interact with the peptide–HLA complex. Some class I molecules also interact with NK cells. The non-classical HLA class I molecules encompass the E, F and G molecules, which are much less polymorphic and which primarily function as ligands for NK cells. Two HLA class 1 α-related chains, MICA and MICB, are polymorphic but do not have a peptide-binding cleft nor do they bind β2m. They are stress

molecules that are up-regulated under certain conditions and function as ligands for the NKG2D activating receptor on NK cells. The HLA class II molecules consist of two heavy chains, α and β, which both include two extracellular domains. Their peptide-binding cleft is formed by their α1 and β1 domains. The class II molecules encompass the DR, DQ and DP series of molecules, encoded by corresponding α and β chain loci in the HLA complex. The DRβ, DQα, DQβ, DPα and DPβ Baf-A1 chains are extremely polymorphic (see next section), whereas the DRα chain is essentially monomorphic. Four different DRβ chains are expressed; DRβ1, DRβ3, DRβ4 and DRβ5. The class II molecules are expressed in specialized antigen-presenting cells such as dendritic cells, where they pick up longer peptide fragments (8–15 amino acids long) primarily from endocytosed exogenous proteins and present them at the cell membrane. Here CD4+ T cells with appropriate T-cell receptors will interact with the peptide–HLA complex. The 4-Mb DNA region of the short arm of chromosome 6 (6p21.