The class I MHC homologue of human cytomegalovirus inhibits attack by natural killer cells

Abstract

Recognition and destruction of virus-infected cells by class I major histocompatibility complex (MHC) restricted cytotoxic T lymphocytes (CTL) is a central part of the immune system's attempts to control and eliminate virus infection. It is therefore not surprising that many viruses have evolved strategies to interfere with the processing and presentation of peptide antigen on class I MHC molecules (reviewed in ref. 1). These mechanisms act to prevent or reduce expression of MHC molecules at the cell surface. However, many natural killer (NK) cells are able to recognize and destroy host cells that no longer express class I MHC molecules (the 'missing self' hypothesis). Thus, any virus-infected cell that has lost cell-surface expression of MHC class I to avoid CTL attack should become susceptible to NK-cell-mediated destruction. We describe here the first example, to our knowledge, of a viral strategy to evade immune surveillance by NK cells.

Multiple sclerosis associates with LILRA3 deletion in Spanish patients

“…22,25 Best known among pathogens that tamper major histocompatibility complex class I expression are herpesviruses, which can alter T-and natural killer-lymphocyte function by subverting the expression of host major histocompatibility complex molecules, or by encoding viral homologues of these. [26][27][28][29][30][31] As all of the polymorphisms of the LRC in chromosome 19, natural killer cells, herpesviruses and HLA class I molecules have been implicated in the susceptibility or pathogenesis of MS, 8,[32][33][34][35][36][37][38][39] it is also of interest to determine whether the genotypic diversity of KIR is associated with MS and whether such an association could explain, by linkage disequilibrium (LD), the reported relationship between MS and deletion of LILRA3.…”

A novel family of Ig-like receptors for HLA class I molecules that modulate function of lymphoid and myeloid cells

“…UL18 may be expressed by HCMV-infected cells in an attempt to engage leukocyte inhibitory receptors and block cell-mediated anti-viral responses [47]. However, it has been difficult to detect cell surface expression of UL18 on transfection of the UL18 gene [48] or during HCMV infection.…”

Human Cytomegalovirus Encodes an MHC Class I-Like Molecule (UL142) That Functions to Inhibit NK Cell Lysis

“…1 and 2 or 9.6 l of 20 M scramble was mixed with 470. 4 l of OPTIMEM (Invitrogen Life Technologies). A total of 4.8 l of LipofectAMINE 2000 (Invitrogen Life Technologies) was mixed with 475.2 l of OPTIMEM and after 5 min at room tempreture the the diluted siRNA and Lipofectamine were gently mixed and incubated at room temperature for 20 min.…”

“…gpUL18 has been shown to bind the inhibitory receptor LIR-1/ILT-2 with 1000 times the affinity of endogenous MHC class I (9). This was originally believed to inhibit NK lysis (4), although this is controversial (10), and whether UL18 provides positive or negative signals to certain NK clones remains unclear.…”