Promiscuous Recognition of a <i>Trypanosoma cruzi</i> CD8⁺ T Cell Epitope among HLA-A2, HLA-A24 and HLA-A1 Supertypes in Chagasic Patients

<div><p>Background</p><p>TcTLE is a nonamer peptide from <i>Trypanosoma cruzi</i> KMP-11 protein that is conserved among different parasite strains and that is presented by different HLA-A molecules from the A2 supertype. Because peptides presented by several major histocompatibility complex (MHC) supertypes are potential targets for immunotherapy, the aim of this study was to determine whether MHC molecules other than the A2 supertype present the TcTLE peptide.</p><p>Methodology/Principal Findings</p><p>From 36 HLA-A2-negative chagasic patients, the HLA-A genotypes of twenty-eight patients with CD8⁺ T cells that recognized the TcTLE peptide using tetramer (twenty) or functional (eight) assays, were determined. SSP-PCR was used to identify the A locus and the allelic variants. Flow cytometry was used to analyze the frequency of TcTLE-specific CD8⁺ T cells, and their functional activity (IFN-γ, TNFα, IL-2, perforin, granzyme and CD107a/b production) was induced by exposure to the TcTLE peptide. All patients tested had TcTLE-specific CD8⁺ T cells with frequencies ranging from 0.07–0.37%. Interestingly, seven of the twenty-eight patients had HLA-A homozygous alleles: A*24 (5 patients), A*23 (1 patient) and A*01 (1 patient), which belong to the A24 and A1 supertypes. In the remaining 21 patients with HLA-A heterozygous alleles, the most prominent alleles were A24 and A68. The most common allele sub-type was A*2402 (sixteen patients), which belongs to the A24 supertype, followed by A*6802 (six patients) from the A2 supertype. Additionally, the A*3002/A*3201 alleles from the A1 supertype were detected in one patient. All patients presented CD8⁺ T cells producing at least one cytokine after TcTLE peptide stimulation.</p><p>Conclusion/Significance</p><p>These results show that TcTLE is a promiscuous peptide that is presented by the A24 and A1 supertypes, in addition to the A2 supertype, suggesting its potential as a target for immunotherapy.</p></div

Micronutrient intake adequacy and depression risk in the SUN cohort study

Purpose The aim of the study was to prospectively assess the association between micronutrient intake adequacy and risk of depression. Methods This dynamic cohort study involves Spanish university graduates (SUN Project). Dietary intake was assessed at baseline and after 10 years of follow-up with a semi-quantitative food frequency questionnaire. Micronutrient intake adequacy for vitamins B1, B2, B3, B6, B12, C, A, D, E, folic acid, zinc, iodine, selenium, iron, calcium, potassium, phosphorus, magnesium and chrome was estimated. Inadequate intake for each nutrient was defined when the intake of the nutrient was below the estimated average requirements (EAR) if available or the adequate intake levels, if EARs were not available. We compared participants with inadequate intake for ≥4 nutrients vs. those with one nutrient. Participants were classified as having incident depression if they had no previous history of depression or antidepressants use at baseline, but they reported during follow-up a new clinical diagnosis of depression by a physician, use of antidepressant drugs, or both. Time-dependent multivariable Cox regression models were fitted. Results After a median follow-up of 8.5 years, 953 new cases of depression were observed among 13,983 participants. Participants with inadequate intake for ≥4 nutrients showed a significantly higher risk of depression [multivariable hazard ratio (HR) = 1.37; 95% confidence interval (CI) 1.01–1.85]. When the analyses were updated with repeated assessments of intakes, the association was attenuated and it was no longer statistically significant (Multivariable HR = 1.11; 95% CI 0.82–1.51). Conclusions Micronutrient inadequacy in four or more micronutrients could exert a moderate role in the development of depression.</p