Human cytomegalovirus and natural killer-mediated surveillance of HLA class I expression: a paradigm of host-pathogen adaptation

Among various strategies to evade the host immune response, some viruses li ke human cytomegalovirus (HCMV) interfere with surface MHC class I expressi on and antigen presentation to T lymphocytes. The ability of natural killer (NK) cells to detect MHC class I molecules through inhibitory receptors ca n be envisaged as an adaptation of the immune system for responding to such pathological alterations. To fulfil that role, rodents use members of the Ly49 C-type lectin superfamily, whereas primates employ killer immunoglobul in-like receptors and the immunoglobulin-Like transcript 2/leucocyte immuno globulin-like receptor-1 receptor. CD94/NKG2 lectin-like heterodimers repre sent the most conserved receptor system for MHC class I molecules; by inter acting with human HLA-E or murine Qa-lb, CD94/NKG2A inhibitory receptors br oadly probe the biosynthesis pathway of other class I molecules. Reciprocal ly, HCMV has developed mechanisms to evade the NK response while modulating HLA class Ia expression. The ability of HCMV to maintain surface levels of HIA-E and to express an HLA class I surrogate (UL18) are herein discussed in the context of the interplay with human NKR systems.