copepodTCR: Identification of Antigen-Specific T Cell Receptors with combinatorial peptide pooling.

T cell receptor (TCR) repertoire diversity enables the orchestration of antigen-specific immune responses against the vast space of possible pathogens. Identifying TCR/antigen binding pairs from the large TCR repertoire and antigen space is crucial for biomedical research. Here, we introduce copepodTCR, an open-access tool for the design and interpretation of high-throughput experimental assays to determine TCR specificity. copepodTCR implements a combinatorial peptide pooling scheme for efficient experimental testing of T cell responses against large overlapping peptide libraries, useful for "deorphaning" TCRs of unknown specificity. The scheme detects experimental errors and, coupled with a hierarchical Bayesian model for unbiased results interpretation, identifies the response-eliciting peptide for a TCR of interest out of hundreds of peptides tested using a simple experimental set-up. We experimentally validated our approach on a library of 253 overlapping peptides covering the SARS-CoV-2 spike protein. We provide experimental guides for efficient design of larger screens covering thousands of peptides which will be crucial for the identification of antigen-specific T cells and their targets from limited clinical material.

Schizophrenia and toxoplasmosis: association with catatonic symptoms.

Introduction: The association between schizophrenia and toxoplasmosis has been demonstrated in a number of studies: the prevalence of schizophrenia is significantly higher in toxoplasmosis positive subjects than in those with T. gondii negative status. However, the clinical significance of this association remains poorly understood. Objectives: To identify clinical phenomena that are typical for toxoplasmosis-associated (T. gondii seropositive) schizophrenia compared to Toxoplasma-seronegative schizophrenia. Methods: A retrospective database analysis of serum samples from 105 inpatients with schizophrenia (ICD-10code: F20; including 55 male patients; mean age of 27.4 6.4 years) was carried out. The clinical examination involved a structured interview including ICD-10 and E. Bleulers criteria for schizophrenia and psychometric tests(Positive and Negative Scales of PANSS). Serum antibodies (IgG) to T. gondii were identified using ELISA. The statistical significance of any differences were evaluated using the non-parametric Mann-Whitney (U) and X2 tests. Results: The proportion of seropositive patients in the sample was 16.2%. Comparing schizophrenia patients, who were seropositive or seronegative for toxoplasmosis, there were no statistically significant differences for the mean total PANSS score, mean PANSS-P, PANSS-N or PANSS-G scores. For the majority of PANSS items, differences were also statistically insignificant, except for G5 and G6mannerism and posturing. Seropositive patients had a higher score for this item than seronegative patients: 3.5 versus 2.1 points (U=389.5; р=0.001). Depression, on the contrary,was less pronounced in seropositive than seronegative patients: 1.4 versus 2.4 points (U=509.5; р=0.023). In addition,in seropositive patients, the frequency of symptoms such as mutism according to ICD-10 criteria for schizophrenia was significantly higher (23.5% versus 3.4%, X2=9.27, р=0.013), and the whole group of catatonic symptoms according to the E. Bleulers criteria for schizophrenia was higher (52.9% versus 28.4%, X2=3.916, p = 0.048). Conclusion: The association between a positive toxoplasmosis status in patients with schizophrenia and catatonic symptoms has been revealed for the first time and should be verified in larger studies.