Natural killer clones recognize specific soluble HLA class I molecules

Abstract

Enhancement of major histocompatibility complex (MHC) class I expression leads to protection from natural killer (NK) cell recognition in several systems. MHC class I gene products are released from the cell surface and can be found in sera as soluble forms. To investigate the possible immunoregulatory role of soluble HLA (sHLA) in NK cell-target recognition, several sHLA antigens were studied for their ability to induce NK cell cytotoxicity modulation. NK cell-target recognition was inhibited by the addition of sHLA during the cytotoxicity assay. Our results indicate that sHLA molecules can down-regulate NK killing at the effector level. Moreover, different NK clones are able to specifically recognize different sHLA antigens. Kp43 molecules seem to be involved in the NK recognition of sHLA-B7.

Increased Level of Soluble HLA Class I Antigens in Systemic Lupus Erythematosus: Correlation with Anti-DNA Antibodies and Leukopenia

“…Several mechanisms have been suggested for production of sHLA, including shedding, differential splicing of mRNA [5] and proteolytic cleavage of membrane-bound HLA class I molecules [6,7]. Experiments have shown that in vitro, sHLA molecules can function as immune regulators, inducing apoptosis of alloreactive T cells [8][9][10][11] and that natural killer cells are downregulated by sHLA-I [12], but the biological functions of circulating sHLA in humans remain unknown.…”

In vivo apoptosis of CD8+ lymphocytes in acute myeloid leukemia patients: involvement of soluble HLA-I and Fas ligand

“…[14][15][16] However, we and others reported that sHLA-I molecules lead to activation-induced apoptosis, in vitro, mediated by synthesis and secretion of FasL and the consequent interaction with Fas expressed by allogeneic and autologous T and natural killer (NK) cells. [17][18][19][20][21] Furthermore, nanomolar concentrations of sHLA-I can prevent both alloreactive clones and primary T-cell cultures from recognizing and lysing their targets. 20 It has been reported that sHLA-I molecules bind to CD8 receptors expressed on cytotoxic effector lymphocytes, that is T and NK cells.…”

Soluble HLA class I molecules induce natural killer cell apoptosis through the engagement of CD8: evidence for a negative regulation exerted by members of the inhibitory receptor superfamily

“…[13][14][15][16] sHLA-I serum levels vary among different individuals and are significantly affected by inflammatory diseases and transplant rejection. [16][17][18][19] sHLA-I has been shown to inhibit cytolytic activity of both alloreactive CTL and NK cells in vitro. [13][14][15][16][17] More recently, it has been reported that sHLA-I, interacting with CD8 molecules, induces apoptosis of CD8 ϩ T lymphocytes on binding of soluble Fas ligand (FasL) to Fas antigen expressed by these cells.…”

“…This phenomenon may play a role in the regulation of antigen-specific immune responses by inducing programmed cell death of effector T lymphocytes. [13][14][15][16][18][19][20][21][22][23][24] However, it is not clear whether sHLA-I delivers an apoptotic signal by interacting with CD8 only or through the simultaneous engagement of CD8 and TCR.…”