Influence of an immunodominant herpes simplex virus type 1 CD8+T cell epitope on the target hierarchy and function of subdominant CD8+T cells

Herpes simplex virus type 1 (hsv-1) latency in sensory ganglia such as trigeminal ganglia (tg) is associated with a persistent immune infiltrate that includes effector memory cd8+t cells that can influence hsv-1 reactivation. in c57bl/6 mice,hsv-1 induces a highly skewed cd8+t cell repertoire,in which half of cd8+t cells (gb-cd8s) recognize a single epitope on glycoprotein b (gb498-505),while the remainder (non-gb-cd8s) recognize,in varying proportions,19 subdominant epitopes on 12 viral proteins. the gb-cd8s remain functional in tg throughout latency,while non-gb-cd8s exhibit varying degrees of functional compromise. to understand how dominance hierarchies relate to cd8+t cell function during latency,we characterized the tg-associated cd8+t cells following corneal infection with a recombinant hsv-1 lacking the immunodominant gb498-505epitope (s1l). s1l induced a numerically equivalent cd8+t cell infiltrate in the tg that was hsv-specific,but lacked specificity for gb498-505. instead,there was a general increase of non-gb-cd8s with specific subdominant epitopes arising to codominance. in a latent s1l infection,non-gb-cd8s in the tg showed a hierarchy targeting different epitopes at latency compared to at acute times,and these cells retained an increased functionality at latency. in a latent s1l infection,these non-gb-cd8s also display an equivalent ability to block hsv reactivation in ex vivo ganglionic cultures compared to tg infected with wild type hsv-1. these data indicate that loss of the immunodominant gb498-505epitope alters the dominance hierarchy and reduces functional compromise of cd8+t cells specific for subdominant hsv-1 epitopes during viral latency. © 2017 rossi et al.