Multiple sclerosis patient-derived spontaneous B cells have distinct EBV and host gene expression profiles in active disease

Soldan, Samantha S.; Su, Chenhe; Monaco, Maria Chiara; Yoon, Leena; Kannan, Toshitha; Zankharia, Urvi; Patel, Rishi J.; Dheekollu, Jayaraju; Vladimirova, Olga; Dowling, Jack W.; Thebault, Simon; Brown, Natalie; Clauze, Annaliese; Andrada, Frances; Feder, Andries; Planet, Paul J.; Kossenkov, Andrew; Schäffer, Daniel E.; Ohayon, Joan; Auslander, Noam; Jacobson, Steven; Lieberman, Paul M.

doi:10.1038/s41564-024-01699-6

Nat Microbiol

2024

DOI: 10.1038/s41564-024-01699-6

|View full text |Cite

Multiple sclerosis patient-derived spontaneous B cells have distinct EBV and host gene expression profiles in active disease

Samantha S. Soldan,

Chenhe Su,

Maria Chiara Monaco

et al.

Help me understand this report

View preprint versions

Search citation statements

Order By: Relevance

Paper Sections

Select...

Citation Types

Supporting

Mentioning

Contrasting

Year Published

2024

Publication Types

Select...

Article3

Relationship

Self Cite0

Independent3

Authors

Journals

Cited by 3 publications

References 70 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Coeliac disease as a model for understanding multiple sclerosis

Drosu,

Bjornevik,

Cortese

et al. 2024

Nat Rev Neurol

View full text Add to dashboard Cite

Coeliac disease as a model for understanding multiple sclerosis

Drosu,

Bjornevik,

Cortese

et al. 2024

Nat Rev Neurol

View full text Add to dashboard Cite

Epstein–Barr virus as a potentiator of autoimmune diseases

Robinson,

Younis,

Love

et al. 2024

Nat Rev Rheumatol

View full text Add to dashboard Cite

CD4 T cells restricted to DRB1*15:01 recognize two Epstein–Barr virus glycoproteins capable of intracellular antigen presentation

Drosu,

Anderson,

Bilodeau

et al. 2024

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Both genetic and environmental factors contribute to multiple sclerosis (MS) risk. Infection with the Epstein–Barr virus (EBV) is the strongest environmental risk factor, and HLA-DR15 is the strongest genetic risk factor for MS. We employed computational methods and in vitro assays for CD4 T cell activation to investigate the DR15-restricted response to EBV. Using a machine learning-based HLA ligand predictor, the EBV glycoprotein B (gB) was predicted to be enriched in epitopes restricted to presentation by DRB1*15:01. In DR15-positive individuals, two epitopes comprised the major CD4 T cell response to gB. Surprisingly, the expression of recombinant gB in a DR15-homozygous B cell line or primary autologous B cells elicited a CD4 T cell response, indicating that intracellular gB was loaded onto HLA class II molecules. By deleting the signal sequence of gB, we determined that this pathway for direct activation of CD4 T cells was dependent on trafficking to the endoplasmic reticulum (ER) within the B cell. We screened seven recombinant EBV antigens from the ER compartment for immune responses in DR15-negative vs. DR15-homozygous individuals. In addition to gB, gH was a key CD4 T cell target in individuals homozygous for DR15. Compared to non-DR15 controls, DR15-homozygotes had significantly higher T cell responses to both gB and gH but not to EBV latent or lytic antigens overall. Responses to gB and gH were slightly elevated in DR15 homozygotes with MS. Our results link MS environmental and genetic risk factors by demonstrating that HLA-DR15 dictates CD4 T cell immunity to EBV antigens.

show abstract

scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.

Contact Info

customersupport@researchsolutions.com

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA

This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.

Blog Terms and Conditions API Terms Privacy Policy Contact Cookie Preferences Do Not Sell or Share My Personal Information

Made with 💙 for researchers

Part of the Research Solutions Family.

Multiple sclerosis patient-derived spontaneous B cells have distinct EBV and host gene expression profiles in active disease

Cited by 3 publications

References 70 publications

Coeliac disease as a model for understanding multiple sclerosis

Coeliac disease as a model for understanding multiple sclerosis

Epstein–Barr virus as a potentiator of autoimmune diseases

CD4 T cells restricted to DRB1*15:01 recognize two Epstein–Barr virus glycoproteins capable of intracellular antigen presentation

Contact Info

Product

Resources

About