Viral Evolution and Transmission

Mauro Malnati

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.

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