Minor histocompatibility (H) Ags are classically described as self-peptides derived from intracellular proteins that are expressed at the cell surface by MHC class I and class II molecules and that induce T cell alloresponses. We have isolated three different T cell populations from a skin biopsy of a patient suffering from acute graft-versus-host disease following sex-mismatched HLA-identical bone marrow transplantation. The first population was: 1) CD4+/CD8+ double-positive; 2) specific for an HLA class I–restricted autosomal Ag; 3) expressed a Tr1 profile with high levels of IL-10, but low IL-2 and IFN-γ; and 4) exerted regulatory function in the presence of recipient APCs. The second was CD8 positive, specific for an HLA class I–restricted autosomally encoded minor H Ag, but was only weakly cytotoxic. The third was CD4 single positive, specific for an HLA-DR7–restricted HY epitope and exerted both proliferative and cytotoxic functions. Identification of the peptide recognized by these latter cells revealed a new human HY epitope, TGKIINFIKFDTGNL, encoded by RPS4Y and restricted by HLA-DR7. In this paper, we show human CD4/CD8 double-positive, acute graft-versus-host disease–protective, minor H Ag–specific regulatory T cells and identify a novel HLA-DR7/ HY T cell epitope, encoded by RPS4Y, a potential new therapeutic target.

Colorectal cancer (CRC) is the leading cause of cancer death worldwide. A crucial process that initiates and progresses CRC is various epigenetic and genetic changes occurring in colon epithelial cells. Recently, huge progress has been made to understand cancer epigenetics, especially regarding DNA methylation changes, histone modifications, dysregulation of miRNAs and noncoding RNAs. In the “epigenome” of colon cancer, abnormal methylation of genes that cause gene alterations or expression of miRNA has been reported in nearly all CRC; these findings can be encountered in the average CRC methylome. Epigenetic changes, known as driving events, are assumed to play a dominant part in CRC. Furthermore, as epigenetic changes in CRC become properly understood, these changes are being established as clinical biomarkers for therapeutic and diagnostic purposes. Progression in this area indicates that epigenetic changes will often be utilized in the future to prevent and treat CRC.

Objective: Allergic asthma is the most frequently observed subtype of individuals with asthma. The effects of serotonin plays in the pathophysiology of asthma has not been clearly determined. Thus, this study aimed to investigate the association between the 5HTR2C gene rs 6318 G>C polymorphism and allergic asthma in pediatric patients in Cyprus. Methods: This study included total number of 177 individuals with 118 control and 59 pediatric patients (43 atopic and 16 non-atopic asthma patient). A skin prick test was performed for each patient to confirm asthma diagnosis and to evaluate atopic status. Genotyping for the 5HTR2C was completed by Real Time-PCR analysis. Results: The genotype distribution frequencies were not in agreement with the Hardy-Weinberg Equilibrium in the patients’ group (p<0.00001). The frequency of the risk allele (allele C) was not significantly different between the patient and control groups (p=0.255). The genotypic distribution between atopic asthma and non-atopic asthma within the patientsts groups was not in agreement with the Hardy-Weinberg Equilibrium (p=0.006). However, risk allele presence showed a statistically significant association with atopy-related asthma (p=0.037). Discussion & Conclusion: Overall, despite the finding of no association between the 5HTR2C rs6318 C allele and childhood asthma, the current results indicated that there is a strong association between the 5HTR2C rs6318 C variant and childhood atopic asthma.

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