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Stern, L.

Publications and source records attributed to Stern, L..

2 recordsLinked to original sources

Immune Cell Profiling Reveals MAIT and Effector Memory CD4+ T Cell Recovery Link to Control of Cytomegalovirus Reactivation after Stem Cell Transplant

Human cytomegalovirus (HCMV) reactivation is a major opportunistic infection after allogeneic haematopoietic stem cell transplantation and has a complex relationship with post-transplant immune reconstitution. Here, we used mass cytometry to comprehensively define global patterns of innate and adaptive immune cell reconstitution at key phases of HCMV reactivation (before detection, initial detection, peak and near resolution) in the first 100 days post-transplant. In addition to identifying patterns of immune reconstitution in those with or without HCMV reactivation, we found mucosal-associated invariant T (MAIT) cell levels at the initial detection of HCMV DNAemia distinguished patients who subsequently developed low-level versus high-level HCMV reactivation. In addition, early recovery of effector-memory CD4+ T cells distinguished low-level and high-level reactivation. Our data describe distinct immune signatures that emerged with HCMV reactivation post-HSCT, and highlight MAIT cell levels at the initial detection of reactivation as a potential prognostic marker to guide clinical decisions regarding pre-emptive therapy.

immunology↗

Human antibody immune responses are personalized by selective removal of MHC-II peptide epitopes

Human antibody responses are established by the generation of combinatorial sequence diversity in antibody variable domains, followed by iterative rounds of mutation and selection via T cell recognition of antigen peptides presented on MHC-II. Here, we report that MHC-II peptide epitope deletion from B cell receptors (BCRs) correlates with antibody development in vivo. Large-scale antibody sequence analysis and experimental validation of peptide binding revealed that MHC-II epitope removal from BCRs is linked to genetic signatures of T cell help, and donor-specific antibody repertoire modeling demonstrated that somatic hypermutation selectively targets the personalized MHC-II epitopes in antibody variable regions. Mining of class-switched sequences and serum proteomic data revealed that MHC-II epitope deletion is associated with antibody class switching and long-term secretion into serum. These data suggest that the MHC-II peptide epitope content of a BCR is an important determinant of antibody maturation that shapes the composition and durability of humoral immunity. HighlightsO_LIAntibody somatic hypermutation selectively removes MHC-II peptide epitopes from B cell receptors. C_LIO_LIAntibodies with lower MHC-II epitope content show evidence of greater T cell help, including class-switching. C_LIO_LIMHC-II peptide epitope removal from a BCR is linked to long-term antibody secretion in serum. C_LIO_LIMHC-II genotype provides a personalized selection pressure on human antibody development. C_LI

immunology↗