As a high-yield NoV cell culture system is still elusive (Jones et al., 2015), NoV VLPs are essential for structural and immunogenicity studies, and they are considered promising vaccine candidates (Blazevic et al., 2011; Atmar et al., 2015). Norovirus infections occur early in life (Hinkula et al., 1995; Nurminen et al., 2011) and antibody seroprevalence reaches almost 100% by Rimonabant hydrochloride adulthood (Jing et XCL1 al., 2000; Carmona-Vicente et al., 2015). IFN- in response to the VLPs of the same origin. In general, stronger T cell responses were induced with the peptides in each donor compared to the VLPs. A CD8+ T cell epitope in the shell domain name of the VP1 (134SPSQVTMFPHIIVDVRQL151) was identified in two subjects, both having human leukocyte antigen (HLA)-A?02:01 allele. To our knowledge, this is the first report using synthetic peptides to study NoV-specific Rimonabant hydrochloride T cell responses in human subjects and identify T cell epitopes. family are highly infectious and cause frequent outbreaks that can be serious to individuals with underlying conditions, the elderly, and young children (Hall et al., 2016). Currently, there is no cure or preventive vaccine available against NoV gastroenteritis. The 7.6 kb-long single-stranded positive-sense RNA genome has three ORFs that encode for the replicase polyprotein (ORF-1), major VP1 capsid protein (ORF-2), and minor capsid protein VP2 (ORF-3; Prasad et al., 1999). NoVs are genetically classified into seven genogroups (GI to GVII), which are further divided into genotypes based on capsid VP1 amino acid sequence diversity (Kroneman et al., 2013; Vinje, 2015). NoV genotypes associated with human infections belong primarily to GI (9 genotypes) and GII (22 genotypes), with a 50% divergence of the VP1 at amino acid-level (Zheng et al., 2006; Kroneman et al., 2013). Variants of the most efficiently evolving GII.4 genotype, with approximately 95% homology in VP1 sequences, have predominated over the last two decades (Bok et al., 2009). VP1 consists of a shell (S) domain name, a hinge region, and a protruding (P) domain name, the latter of which is usually further divided into the P1 and extremely variable P2 subdomains; they contain sites important for host cell conversation (Cao et al., 2007). Ninety dimeric VP1 proteins form the outer layer of the icosahedral virus particle, which can vary in size from 27 to 40 nm, depending on the genotype (Vinje, 2015). VLPs are self-assembled by the recombinant capsid protein VP1. As a high-yield NoV cell culture system is still elusive (Jones et al., 2015), NoV VLPs are essential for structural and immunogenicity studies, and they are considered promising vaccine candidates (Blazevic et al., 2011; Atmar et al., 2015). Norovirus infections occur early in life (Hinkula et al., 1995; Nurminen et al., 2011) and antibody seroprevalence reaches almost 100% by adulthood (Jing et al., 2000; Carmona-Vicente et al., 2015). Multiple sequential infections by genetically distinct NoV strains have been reported to occur frequently, especially in young children (Saito et al., 2014; Rimonabant hydrochloride Blazevic et al., 2015b). According to most studies, the duration of protection in adults is relatively short and limited to genetically similar virus strains (Wyatt et al., 1974; Johnson et al., 1990; Simmons et al., 2013). There is controversy over the correlates of protective NoV immunity and the length and specificity of the protection, which is complicated by the genetic diversity of NoVs (Siebenga et al., 2009; Vinje, 2015) and differences in the pre-existing NoV immunity of humans (Lindesmith et al., 2010, 2015). Furthermore, the distinctive expression pattern of polymorphic HBGAs affects individual susceptibility to NoV infections (Lindesmith et al., 2013). HBGAs, found, e.g., on the respiratory and gastrointestinal tract surface epithelia and in bodily secretions, are recognized and bound by NoV particles in a genotype-specific manner (Uusi-Kerttula et al., 2014) and putatively serve as the initiation site for NoV infection (Hutson et al., 2002; Huang et al., 2003; Cao et al., 2007). Serum IgG antibody titers blocking NoV VLP binding to HBGA have been most frequently associated with protection from NoV infection and disease (Reeck et al., 2010; Nurminen et al., 2011; Malm et al., 2014; Atmar et al., 2015). Humoral immunity to homotypic strains is efficiently elicited (Malm et al., 2014), and broadly cross-reactive NoV-specific IgG antibodies are found after NoV exposure (Rockx et al., 2005; Lindesmith et al., 2010; Malm et al., 2014). However, the induction of cross-protective antibodies capable of blocking NoV VLP-HBGA binding interaction have been observed only to a Rimonabant hydrochloride certain degree between the different genotypes of the GII or GI genogroups, but not across the genogroups (Reeck et al., 2010; Atmar et al., 2015; Blazevic et al., 2015c). Additionally, mucosal IgA responses have been associated with the blocking activity of NoV-HBGA binding (Tamminen et al., 2016) and protection from infection and NoV gastroenteritis (Lindesmith et al., 2003; Ramani et al., 2015). While most NoV immunity studies have focused on humoral immune responses (Ramani.