The Role of HLA-Class Ib Molecules in Immune-Related Diseases, Tumors, and Infections 2016

HLA-class I family includes highly polymorphic HLA-class Ia molecules (HLA-A, HLA-B, and HLA-C), which play a central role in adaptive immunity, and “nonclassical” HLA-class Ib molecules (HLA-E, HLA-F, HLA-G, and HLA-H), characterized by a limited polymorphism and a few alleles that encode a small number of functional proteins. Both types of HLA-class I molecules can bind peptides generated from cytosolic antigens and present them to specific CD8+ T lymphocytes. However, the main function of HLA-class Ib molecules is the modulation of immune responses, both in physiological and in pathological conditions. In contrast, nonclassical major histocompatibility complex (MHC) class I chain related (MIC) molecules show homology with classical human leukocyte antigen (HLA) molecules, but they do not bind beta-2 microglobulin and peptides. Expression of MIC proteins is upregulated on the cell surface in response to stress, and these molecules can interact with the activating natural killer cell receptor NKG2D, which is expressed by many cells of the immune syste