Machine learning analysis of the T cell receptor repertoire identifies sequence features of self-reactivity.

The T cell receptor (TCR) determines specificity and affinity for both foreign and self-peptides presented by the major histocompatibility complex (MHC). Although the strength of TCR interactions with self-pMHC impacts T cell function, it has been challenging to identify TCR sequence features that predict T cell fate. To discern patterns distinguishing TCRs from naive CD4 T cells with low versus high self-reactivity, we used data from 42 mice to train a machine learning (ML) algorithm that identifies population-level differences between TCRβ sequence sets.

The splenic T cell receptor repertoire during an immune response against a complex antigen: Expanding private clones accumulate in the high and low copy number region.

Large cellular antigens comprise a variety of different epitopes leading to a T cell response of extreme diversity. Therefore, tracking such a response by next generation sequencing of the T cell receptor (TCR) in order to identify common TCR properties among the expanding T cells represents an enormous challenge. In the present study we adapted a set of established indices to elucidate alterations in the TCR repertoire regarding sequence similarities between TCRs including VJ segment usage and diversity of nucleotide coding of a single TCR.

Colorectal Cancer Progression Is Potently Reduced by a Glucose-Free, High-Protein Diet: Comparison to Anti-EGFR Therapy.

To enable rapid proliferation, colorectal tumor cells up-regulate epidermal growth factor receptor (EGFR) signaling and aerobic glycolysis, resulting in substantial lactate release into the tumor microenvironment and impaired anti-tumor immune responses. We hypothesized that a nutritional intervention designed to reduce aerobic glycolysis may boost the EGFR-directed antibody (Ab)-based therapy of pre-existing colitis-driven colorectal carcinoma (CRC). CRC development was induced by azoxymethane (AOM) and dextran sodium sulfate (DSS) administration to C57BL/6 mice.

Effects of sleep on the splenic milieu in mice and the T cell receptor repertoire recruited into a T cell dependent B cell response.

Sleep is known to improve immune function ranging from cell distribution in the naïve state to elevated antibody titers after an immune challenge. The underlying mechanisms still remain unclear, partially because most studies have focused on the analysis of blood only. Hence, we investigated the effects of sleep within the spleen in female C57BL/6J mice with normal sleep compared to short-term sleep-deprived animals both in the naïve state and after an antigen challenge.