Table 1.

Advantages and disadvantages of approaches to HHV-6 epitope discovery.

Approach	Advantages	Disadvantages
Selected proteins based on human cytomegalovirus homology	Enables scanning for epitopes in reasonable blood volumes from persons with diverse HLA types	Leaves most HHV-6 proteins unexplored for epitopes
Epitope prediction based on selected HLA restrictions	Provides an efficient method to scan entire viral proteome space for epitopes	HLA-binding affinity alone is an inconsistent predictor of actual immunogenicity
		Leaves unexplored epitopes recognized by other HLA alleles
Ex vivo T cell responders	High precision: relative abundances and phenotype closely approximate in vivo biology	Low sensitivity: HHV-6-specific T cells are rare and frequently below the lower limit of detection
In vitro expanded T cell responders	High sensitivity: can detect infrequent T-cell specificities and define a detailed hierarchy of population prevalence	Low precision: expansion process could skew proportions of T-cell clonotypes and/or change their gene expression profiles