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Traditionally, the MHC is divided into the classes containing groups of genes with related functions; the MHC class I and II genes encode for human leukocyte antigens (HLA), proteins that are displayed on the cell surface. In humans, MHC class I molecules com‐ prise the classical (class I-a) HLA-A, -B, and -C, and the non-classical (class I-b) HLA-E, F, -G and – H (HFE) molecules (Pietra et al., 2009). Both categories are similar in their mechanisms of peptide binding and presentation and in the induced T-cell responses (Rodgers and Cook, 2005). The most remarkable feature of MHC class I-b molecules is their highly conserved nature (van Hall et al., 2010). In contrast with class Ia molecules they have been under a distinct selective pressure, exhibiting very low levels of allelic polymor‐ phism (Strong et al., 2003). Classical MHC class I gene transcription is mediated by several cis-acting regulatory elements, in the proximal promoter region (Gobin and van den Elsen, 2000). Those elements determine the constitutive and cytokine induced expression levels of the molecule (Gobin and van den Elsen, 2000).

HLA-E, HLA-F and HLA-G — The Non-Classical Side of the MHC Cluster