Presentation of an Immunodominant Immediate-Early CD8+ T Cell Epitope Resists Human Cytomegalovirus Immunoevasion

Control of human cytomegalovirus (hcmv) depends on cd8+ t cell responses that are shaped by an individual's repertoire of mhc molecules. mhc class i presentation is modulated by a set of hcmv-encoded proteins. here we show that hcmv immunoevasins differentially impair t cell recognition of epitopes from the same viral antigen,immediate-early 1 (ie-1),that are presented by different mhc class i allotypes. in the presence of immunoevasins,hla-a- and hla-b-restricted t cell clones were ineffective,but hla-c*0702-restricted t cell clones recognized and killed infected cells. resistance of hla-c*0702 to viral immunoevasins us2 and us11 was mediated by the alpha3 domain and c-terminal region of the hla heavy chain. in healthy donors,hla-c*0702-restricted t cells dominated the t cell response to ie-1. the same hla-c allotype specifically protected infected cells from attack by nk cells that expressed a corresponding hla-c-specific kir. thus,allotype-specific viral immunoevasion allows hcmv to escape control by nk cells and hla-a- and hla-b-restricted t cells,while the virus becomes selectively vulnerable to an immunodominant population of hla-c-restricted t cells. our work identifies a t cell population that may be of particular efficiency in hcmv-specific immunotherapy. © 2013 ameres et al.