Abstract
Natural killer (NK) cells are effector lymphocytes of the innate immune system that are able to mount a multifaceted antiviral response within hours following infection. This is achieved through an array of cell surface receptors surveilling host cells for alterations in human leukocyte antigen class I (HLA-I) expression and other ligands as signs of viral infection, malignant transformation, and cellular stress. This interaction between HLA-I ligands and NK-cell receptor is not only important for recognition of diseased cells but also mediates tuning of NK-cell-effector functions. HIV-1 alters the expression of HLA-I ligands on infected cells, rendering them susceptible to NK cell-mediated killing. However, over the past years, various HIV-1 evasion strategies have been discovered to target NK-cell-receptor ligands and allow the virus to escape from NK cell-mediated immunity. While studies have been mainly focusing on the role of polymorphic HLA-A, -B, and -C molecules, less is known about how HIV-1 affects the more conserved, non-classical HLA-I molecules HLA-E, -G, and -F. In this review, we will focus on the recent progress in understanding the role of non-classical HLA-I ligands in NK cell-mediated recognition of HIV-1-infected cells.
Highlights
Untreated HIV-1 infection will lead to progressive, severe, and mostly fatal immune deficiency in the vast majority of individuals
While numerous studies have established a role for the killer-cell immunoglobulin-like receptors (KIRs) interaction with classical human leukocyte antigen class I (HLA-I) in HIV-1, recent advances have increased our understanding of non-classical human leukocyte antigen (HLA)-E, -F, and -G in HIV-1 infection
HLA-F was identified as a ligand for KIR3DS1, which is prominently associated with HIV-1 disease control
Summary
Untreated HIV-1 infection will lead to progressive, severe, and mostly fatal immune deficiency in the vast majority of individuals. As KIRs are predominantly expressed on NK cells, Martin et al.’s first report associating a KIR to an outcome in HIV-1 infection [22] triggered multiple studies on NK-cell functionality attempting to elucidate the underlying protective mechanism of KIR3DS1 in combination with HLA-Bw4I80 in HIV-1 disease.
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