New insights into childhood Vernal keratoconjunctivitis-associated factors.

The purpose of this study was to test for detectable serum levels of antibodies usually associated with immune-related diseases in children with Vernal keratoconjunctivitis (VKC) and seek for their family history of allergies and autoimmune disorders. The association of human leukocyte antigens (HLA) with VKC was also investigated. We enrolled 181 VKC children and assessed total and specific IgE, antithyroglobulin (AbTG), antithyroidperoxidase (AbTPO), antitransglutaminase (tTG), and antinuclear antibodies (ANA) by standard procedures. Class I and II HLA typing was also carried out following standard protocols, and it was compared with that of healthy subjects. Patients were positive for AbTG (22%), AbTPO (14.6%), and ANA (15.8%), and AbTG positivity was associated with VKC severity (mean ocular score ± SD positive vs. negative: 6.56 ± 2.1 vs. 4.82 ± 2.1; p = 0.03). We found that 12.2% of VKC cases had a positive family history for psoriasis, 6.4% for other cases of VKC, and 5.2% for thyroiditis, while 50.2% of them were atopic. The expression of HLA class I B37 was significantly higher in VKC patients than in controls (7.1% vs. 2.1%, p = 0.04), although not confirmed after multiple antigens testing analysis. Our study suggests a role of common components associated with immune-based diseases in the clinical expression of VKC.

Broad CD8+ T cell cross-recognition of distinct influenza A strains in humans.

Newly-emerged and vaccine-mismatched influenza A viruses (IAVs) result in a rapid global spread of the virus due to minimal antibody-mediated immunity. In that case, established CD8+ T-cells can reduce disease severity. However, as mutations occur sporadically within immunogenic IAV-derived T-cell peptides, understanding of T-cell receptor (TCRαß) cross-reactivity towards IAV variants is needed for a vaccine design. Here, we investigate TCRαß cross-strain recognition across IAV variants within two immunodominant human IAV-specific CD8+ T-cell epitopes, HLA-B*37:01-restricted NP338-346 (B37-NP338) and HLA-A*01:01-restricted NP44-52 (A1-NP44). We find high abundance of cross-reactive TCRαß clonotypes recognizing distinct IAV variants. Structures of the wild-type and variant peptides revealed preserved conformation of the bound peptides. Structures of a cross-reactive TCR-HLA-B37-NP338 complex suggest that the conserved conformation of the variants underpins TCR cross-reactivity. Overall, cross-reactive CD8+ T-cell responses, underpinned by conserved epitope structure, facilitates recognition of distinct IAV variants, thus CD8+ T-cell-targeted vaccines could provide protection across different IAV strains.