University of Massachusetts Medical School Faculty Publications

UMMS Affiliation

Department of Pathology

Publication Date

2021-01-17

Document Type

Article Preprint

Disciplines

Amino Acids, Peptides, and Proteins | Hemic and Immune Systems | Immunity | Immunology of Infectious Disease | Immunopathology | Investigative Techniques

Abstract

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.

Keywords

Immunology, B cell development, antibodies, B cell sequencing, somatic hypermutation, MHC-II peptide epitopes

Rights and Permissions

The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.

DOI of Published Version

10.1101/2021.01.15.426750

Source

bioRxiv 2021.01.15.426750; doi: https://doi.org/10.1101/2021.01.15.426750. Link to preprint on bioRxiv.

Comments

This article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review.

Full author list omitted for brevity. For the full list of authors, see article.

Journal/Book/Conference Title

bioRxiv

Creative Commons License

Creative Commons Attribution-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-No Derivative Works 4.0 License.

Share

COinS