Non-Classical MHC Class Ib Molecules and their Receptors–Role in Allogeneic Transplantation of Hematopoietic Stem Cells

Abstract

HLA-E, HLA-G, and major histocompatibility complex class I-related chain A and B (MICA and MICB) proteins belong to human non-classical Major Histocompatibility Complex (MHC) class Ib molecules. These molecules are well known as powerful modulators of the immune response. The majority of the mentioned proteins interact exclusively with receptors from the CD94/NKG2 c-type lectin family. The peptide-presenting HLA-E molecule is recognized by the NKG2A or NKG2C receptor, triggering a signal cascade leading to inhibition or activation of immune cell activity, respectively. Another member of this family is the NKG2D receptor that interacts with the MICA/B proteins, transducing signals that result in activation of immune cells. This article discusses the current knowledge in regard to the genetic properties and physiological functions of the molecules HLA-E and MICA/B as well as the CD94/NKG2 receptors in the context of the potential role of the signaling pathways they constitute in the outcome of hematopoietic stem cell transplantation. Furthermore, the possible role of HLA-G, also a member of the non-classical MHC class Ib family, is considered.