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Kister, I.

Publications and source records attributed to Kister, I..

2 recordsLinked to original sources
bioRxiv2025

Persistent Classical and Atypical Memory B Cells Underlie Heterogeneous Vaccine Responses in Ocrelizumab-Treated Multiple Sclerosis

Background and ObjectivesPatients with multiple sclerosis (pwMS) treated with ocrelizumab (OCR), a B-cell-depleting therapy, exhibit heterogeneous humoral responses to SARS-CoV-2 mRNA vaccination. The mechanisms underlying this variability remain incompletely understood. We performed a longitudinal analysis of B-cell subset dynamics and antigen-specific T cell responses in OCR-treated pwMS and healthy controls to determine how immune cell composition, timing of OCR infusion, and lymphocyte dynamics influence humoral response outcomes. MethodsBased on post-vaccination anti-Spike IgG titers measured by multiplex bead immunoassay, pwMS were categorized as super-responders (SR), responders (R), or non-responders (NR). A 35-marker spectral flow cytometry panel was used to characterize T- and B-cell subsets longitudinally, at baseline and following stimulation with a SARS-CoV-2 peptide pool. ResultsCD4+ and CD8+ T cell populations were preserved across OCR-treated pwMS, and SARS-CoV-2-specific T cells remained detectable for more than 6 months after vaccination. In contrast, residual B-cell subset composition distinguished responders from non-responders. DN2-like B cells (CD19+CD27-IgD-T-bet+CD11c+CXCR5-) persisted despite repeated OCR infusions and were enriched in SR compared with NR. Repletion of mature naive B cells in peripheral blood correlated with time since last OCR infusion and with stronger humoral immune responses. ConclusionsB-cell subsets that resist OCR-mediated depletion may contribute to vaccine responsiveness in OCR-treated pwMS. Altered repletion kinetics of naive B cell subsets in non-responders suggest that specific B-cell populations may serve as predictive biomarkers of vaccine-induced humoral immunity, despite preserved T-cell responses.

immunology↗
bioRxiv2025

A common network of residue-residue contacts underlies peptides' interactions with MHC class II complex

The formation of a stable peptide-MHC class II complex is a critical step in the adaptive immune response. In this work, we investigate the residue-residue contacts that anchor the peptide between the alpha and beta chains of MHC II and examine whether such anchoring residue-residue contacts are shared among different peptide-MHC II complexes. We hypothesize that there is a similarity between the map of contacts of antigenic peptides with the alpha and beta chains of MHC II and the map of contacts of the "natural" complex of MHC II with the CLIP - the fragment of the gamma chain. Thus, the CLIP-MHC II complex - specifically, PDB structure 3PDO - was taken as the prototype for peptide-MHC II interaction. To compare the contact maps between the prototype structure and antigenic peptides/MHC II in 14 crystal structures, we developed a unified numbering system for residues in peptide-MHC II complexes. Using this unified residue numbering system, we show that approximately half of the CLIP-MHC II residue-residue contacts have analogs in structures that involve different antigenic peptides and different MHC II (HLA-DR, HLA-DQ, and mouse A/B) alpha and beta chains. We present here this common network of contacts that underlies peptide/MHC class II interactions, as well as the structural and physicochemical characteristics of these contacts. Based on these shared characteristics, we propose criteria for the specificity of antigenic peptide loading into MHC II, whereby one can predict whether a particular peptide fragment will bind to MHC II as well as the likely localization of the fragment within the peptide binding groove of MHC II.

immunology↗