HLA-F on autologous HIV infected cells activates primary NK cells expressing the activating killer immunoglobulin-like receptor KIR3DS1 [Cellular Response to Infection]

IMPORTANCE This manuscript investigates a mechanism which can underly Preliminary studies demonstrating that carriage of the KIR3DS1 homozygous genotype is more frequent among HIV exposed seronegative subjects than among HIV vulnerable people. Carriage of the genotype is associated with a low probability of HIV infection. The protective mechanism involves the interaction of HLA-F on CD 4 cells infected with replication competent HIV together with all the activating NK receptor, KIR3DS1. This interaction contributes to the activation of KIR3DS1+ NK cells for secretion of cytokines and chemokines with anti-HIV activity. One of these could be that the secretion of CCL4, which binds and blocks CCR5, the co-receptor to get HIV entry of HIV into fresh cells. In the setting of an exposure to HIV, in coming HIV-infected cells dispersing HLA-F rapidly activate KIR3DS1+ NK cells to elicit anti-HIV activity. Exclusive gating blocking and strategies experiments support the belief which the HLA-F/KIR3DS1 interaction is sufficient to activate NK cell functions.
HIV-exposed seronegative KIR3DS1 homozygotes have a lower chance of HIV infection. HLA-F is the ligand for the activating NK cell receptor (NKR) KIR3DS1. HLA-F is expressed on HIV-infected CD4 T cells. Co-culture of sprinkled, HIV-infected CD-4 (siCD4) T cells with NK cells activated a higher frequency of KIR3DS1+ compared to KIR3DS1 NK cells in KIR3DS1 homozygotes to elicit anti-HIV functions such as CCL4, IFN- and CD107a expression. This is actually the case whether KIR3DS1+/ NK cells were examined inclusively or only by gating outside NK cells co-expressing that the NKRs, KIR2DL1/L2/L3, 3DL2, KIR2DS1/S2/S3/S5, NKG2A and ILT2. Blocking the interaction of HLA-F on siCD4 cells using KIR3DS1 on exclusively gated KIR3DS1+ NK cells with KIR3DS1-Fc chimeric protein or a HLA-F specific monoclonal antibody, reduced the frequency of actuated KIR3DS1+ cells compared to control conditions. KIR3DS1+ NK cell activation by HIV-infected CD4 cells may impair the decreased probability of KIR3DS1 homozygotes to HIV illness.

Like it.? Share it:

Leave a Reply

Your email address will not be published. Required fields are marked *

This site uses Akismet to reduce spam. Learn how your comment data is processed.