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

摘要

HLA-class Ib family include HLA-E, -F, -G, and -H molecules that, in contrast with high polymorphic HLA-class Ia molecules (HLA-A, -B, and -C), display a limited polymorphism, with a small number of alleles encoding limited functional proteins. Similar to HLA-class Ia molecules, HLA-class Ib molecules bind peptides generated from cytosolic antigens and present them to CD8~+ T lymphocytes, but their main function is the regulation of immune responses, both in physiological and pathological conditions. HLA-G, the best characterized HLA-Ib molecule, is expressed on fetal cytotrophoblast cells during pregnancy and abrogates maternal NK cell cytotoxicity against fetal tissues. However, HLA-G is also expressed (or released as soluble molecules) by different cells and tissues in pathological contexts such as tumors, grafted organs, pathogen-infected cells, and inflammatory tissues. HLA-G interacts with specific receptors on T and B lymphocytes, NK cells, neutrophils, and antigen presenting cells, inhibiting their function. HLA-E is virtually expressed by all nucleated cells and binds peptides derived from HLA-class I molecules leader sequence. In physiological conditions, it interacts with CD94/NKG2A inhibitory receptor on NK cells, inhibiting their cytotoxicity against cells displaying normal HLA-class I molecules expression.