The IP of the Immunogenetics and Histocompatibility group at the IIS Puerta de Hierro maintains a continuous track record of basic and translational research funded through public calls since 1995. Given its small size, the group’s scientific output is notable in terms of both the number and quality of publications, especially in terms of its visibility or real impact (IP H index: 29; 246 citations/year on average between 2012 and 2016), and because it combines clinical and research activities.

The group specializes in immunogenetics and lymphocyte differentiation receptors, with special attention to their role as biomarkers for viral infections, transplantation and anti-tumor immunotherapy, collaborating with other national and international immunology groups, as well as with clinical groups for translational objectives. Currently, the candidate is IP of three multicenter coordinated projects funded in highly competitive calls (SAF-Retos Plan Nacional I+D+i, EU-FP7 EraNet and Fundación AECC), which relate to NK cells in viral infections, transplantation and anti-tumor immunotherapy.

The group has contributed substantially to the knowledge of KIR receptors, which allow NK cells to monitor the normal expression of HLA molecules. In the late 1990s, the PI discovered the existence of several genes and pseudogenes in this family, including the last functional KIR described, KIR2DL5. He also demonstrated its polymorphism; its duplication in the human genome; its involvement in asymmetric recombinations that increase genetic diversity; and the epigenetic silencing or intracellular retention of some of the gene's alleles. In collaboration with Miguel López-Botet's group, he generated the only monoclonal antibody specific to this molecule; the transfer of these results has been successfully achieved, as the antibody is under commercial exploitation, licensed on a limited basis by several biotechnology companies (Beckman-Coulter, Becton-Dickinson, Miltenyi and others). Tools have also been developed for research into the receptor, such as soluble and chimeric reporter forms, which are expected to help determine the molecules it interacts with and its role in the immune response.

In terms of translational objectives, the group is currently interested in the contribution of NK cells to responses against Herpesviruses. In the first area, over the last decade we have carried out studies that have identified immunogenetic variables correlated with the risk of symptomatic infections from Herpes simplex virus type I, several of which are related to NK cell activity, including both its natural activity and antibody-dependent cell-mediated cytotoxicity (ADCC). We have also actively collaborated in a line of research led by Dr López-Botet on the interaction between NK cells and human cytomegalovirus, which manifests as the expansion, to a variable degree, of a subpopulation characterised by high expression of the HLA-E receptor formed by the CD94:NKG2C heterodimer. Our participation in this line of research is helping to identify the immunogenetic variables that modulate and control this expansion. The phenomenon has clinical relevance, as the degree of expansion of this subpopulation appears to modify control of the virus, with consequences for the clinical course of transplants and other immunodeficiency situations. Finally, another researcher from the institution, Dr Natalia Gómez Lozano, collaborates with the group, studying immunogenetic factors in tumours and lymphoproliferative syndromes associated with Epstein-Barr virus. This covers three of the most prevalent herpesviruses in our population (HSV-1, CMV and EBV), and will allow us to study the interactions between the immune responses against them.

Furthermore, the group is interested in exploiting the biological properties of NK cells to improve antitumour immunotherapy, and is taking part in a coordinated project for this purpose; our group monitors the immunogenetic variables that affect the effectiveness of effector cells. In this same field, the PI has collaborated as a scientific advisor with the French company Emercell (http://www.emercell.com) in achieving its objectives (generation of allogeneic NK cells for anti-leukaemia therapy).