Viral Evolution and Transmission
Mauro Malnati
Email: malnati.mauro@hsr.it
Location: DIBIT1, Floor 2s, Room 3
Research Associate, Viral evolution and transmission
Brief Introduction
In human, cytotoxic activity of NK cells results from a fine balance of both activating and inhibitory signals that depend on the killer immunoglobulinlike receptors (KIRs), whose ligands are the human leukocyte antigen (HLA) class I molecules. KIRs consist of two (KIR2D) or three (KIR3D) extracellular immunoglobulin-like domains, a stem region, a transmembrane domain and a cytoplasmic tail. Commonly, inhibitory KIRs (iKIRs) possess a long (L) cytoplasmic tail (e.g. KIR2DL) and activating KIRs (aKIRs) a short (S) cytoplasmic one (e.g. KIR2DS)24. The 16 KIR genes are located on the chromosome 19q13.4 within the human leucocyte complex and comprise the following: 6 genes encoding aKIRs (2DS15 and 3DS1); 7 genes encoding iKIRs (2DL1-3, 5 and 3DL1-2); KIR2DL4, which exerts both inhibitory and activating activity; and 2 pseudogenes (2DP1 and 3DP1)25. Composition of KIRs may be complex, thus, two haplotypes (A and B) and genotypes (AA and Bx, where x can be A or B) have been reported for KIR based on gene content. Insofar, over 500 different Bx genotypes have been described.
Research Activity
- The main focus of my research is to understand the role that KIRs play in counteracting viral infections and modulating T and NKcell immune responses in the solid organ transplant setting and in autoimmune disorders such as Type 1 Diabetes.
- Regarding viral infection we demonstrated that a complex genotype displaying high expression of HLAC alleles belonging to the C2 group and their KIR 2DS receptors ligands is a hallmark of some individuals infected by HIV-1 that successfully control viral replication termed Elite controllers (EC) These findings suggest a novel role for activating 2DS KIRs expressed on both NK and CD8+ T-cells in the control of HIV-1 viremia. We are extending now are observations to one another interesting category of HIV-1 infected individuals termed post treatment controllers (PTCs) of infection after therapy interruption in order to identify predictive biomarkers of these special conditions of HIV-1 infection and disease progression.
- Regarding the transplant setting of ßcells we are investigating whether the early loss of islets or other sources of insulinproducing cells may be the consequence of KIR/HLA mismatches leading to loss of the inhibitory signals that counterbalance the NKp30 and DNAM-1 activating axes on NK cells.
1987 MD, Medicine and Surgery, University of Genoa
1988 NA, Immunology, University of Genoa
1991 Certified Pediatrician, Univeristy of Genoa
1992 Visiting Fellow, Laboratory of Immunogenetics NIH-NIAID
1992-1994 Visiting Associate, Lab of Immunogenetics NIH-NIAID, Bethesda, USA
1995-2009 Senior Scientist, Dept of Biotechnology, IRCCS Ospedale San Raffaele, Milan
2009-2019 Acting Chief, Division of Immunology, IRCCS Ospedale San Raffaele, Milan
2019-date PI, Division of Immunology, IRCCS Ospedale San Raffaele, Milan
1989-1992 Awarded of a Fogarty International Fellowship, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
1995-2001 Member of the Scientific committee “workshop Italiano di PCR quantitativa”
2000-2001 Italian delegate for the European Committee of Normation (CEN) working group 275/WG11
2013-now Associate professorships in Clinical Microbiology and Clinical Pathology
Francesca Sironi, Technician - sironi.francesca@hsr.it