HLA-G molecules in infection and autoimmune diseases

Abstract

Human leukocyte antigen-G (HLA-G) is a non-classical HLA class I molecule that differs from classical HLA class I molecules for low allelic polymorphism and restricted tissue distribution. In physiological conditions HLA-G molecules are expressed on trophoblast at the fetal-maternal interface and other sites of immune privilege, such as thymus and cornea, where have an important role in the maintenance of a tolerogenic condition. In fact, HLA-G regulates the immune response through its immune-modulatory and anti-inflammatory function on both innate and adaptive immunity. HLA-G molecules are expressed as membrane bound and soluble isoforms (mHLA-G, sHLA-G) that bind and activate immune-inhibitory receptors (ILT2, ILT4, KIR2DL4) expressed on immune cells. Recently, HLA-G molecule has been shown to have an important implication in different pathological situations, such as infections and autoimmune diseases, where HLA-G shows aberrant expression and specific HLA-G gene polymorphisms correlate with disease severity and outcome. Moreover, HLA-G could be up-modulated and used as a immune-escape mechanism by virus and tumours. On the basis of this knowledge, HLA-G may exhibit two distinct effects in pathological conditions: it could be protective in Th1-based inflammatory and autoimmune diseases or it could be detrimental in tumors or infectious diseases. The aim of this thesis is to investigate the role of HLA-G mlecules in different pathological conditions: microbial infections and autoimmune diseases.