Interactions between Immunoglobulin like receptors and the Peptidome in the Allogeneic Hematopoietic Stem Cell Transplantation in the Cytomegalovirus context. A mini review.

Abstract

The Natural Killer cells are innate lymphoid cells that play essential roles in defense against viral and parasitic infections, elimination of tumor cells, regulation of adaptive immunity through cytotoxicity, and cytokine secretion. Fundamental knowledge about the regulation of Natural Killer cells can be applied to study their function in patients undergoing hematopoietic stem cell transplantation, with or without Cytomegalovirus reactivation. The function of Natural Killer cells is governed by a repertoire of receptors responsible for initiating intracellular activating or inhibitory signaling. The balance of this signaling directs the cytotoxic activity of these cells, as well as cell proliferation and cytokine release.Understanding the interaction of receptors expressed on the surface of Natural Killer cells with their ligands expressed on target cells is a topic of discussion in the context of alloreactivity and the graft-versus-leukemia effect in transplant patients. Recent investigations have shown that KIR/HLA interactions go beyond affinity and describe that many of them depend on the peptide being presented by the HLA at that moment. Analysis of the peptidome (HLA class I + bound peptide) has demonstrated that some Natural Killer cell receptors are peptide-dependent. Therefore, understanding these interactions by considering the entire Natural Killer cell receptor + HLA class I + peptide complex is crucial in the reestablishment of immune cells after hematopoietic stem cell transplantation, especially in the context of Cytomegalovirus reactivation, which is very common in these patients. Hence, the aim of this study is to deepen our understanding of the specificity of interactions between human Natural Killer cell KIR receptors and the peptidome in the context of Cytomegalovirus reactivation after allogeneic, related, HLA-compatible hematopoietic stem cell transplantation without T-cell depletion. For the analysis of interactions between Natural Killer cell receptors and peptidomes, specific peptide libraries for HLA class I alleles will be created to evaluate the specificities of interactions between KIR + HLA class I + peptide.