Multiple sclerosis

HLA-DRB1*15:01

Multiple sclerosis is an inflammatory disease of the central nervous system. The largest genetic contribution comes from HLA-DRB1*15:01. Together with a past Epstein-Barr virus infection, the strongest known environmental factor, this yields a model of predisposition plus trigger.

WHERE IS THE MYELIN PEPTIDE (MBP) SHOWN ON HLA-DR15? SITE MBP ON HLA-DR15 EBV-infected B cell presented MS brain tissue the same peptide Healthy B cell absent Thymus absent Because the peptide is absent in the thymus, the autoreactive CD4 T cell is not deleted there. It later responds in the blood to exactly this MBP peptide and attacks myelin. Source: Wang et al., Cell 2026. EBV changes what HLA-DR15 displays; the same myelin fragments appear in MS brain.

Predisposition meets trigger

DRB1*15:01 changes which peptides are presented to T cells and favours autoreactive responses against components of the myelin sheath. A large longitudinal study showed that practically all MS cases had a preceding EBV infection. Molecular mimicry between EBV proteins and self structures is a discussed mechanism.

How virus and gene act together

A 2026 study supplies a concrete mechanism beyond pure mimicry. When EBV infects a B cell, it alters the cell's gene activity and thereby which fragments end up on the DR15 molecules, the carrier of DRB1*15:01. Among them appear fragments of myelin basic protein (MBP), the body's own myelin. The same MBP fragments were found on EBV-infected B cells and in MS brain tissue, but not on healthy B cells or in the thymus. Precisely because they are missing in the thymus, the matching T cells are not deleted there; CD4 T cells from DR15 patients later responded to exactly these peptides. Trigger and predisposition thus meet at a single point.

Context

DRB1*15:01 is common and raises risk only moderately; the vast majority of carriers never fall ill. The marker explains predisposition, not course. Genome presents the HLA type as technical evidence and points to the EBV context, without diagnostic claim.

What Genome measures. Presence of the risk allele HLA-DRB1*15:01 and of protective class I types (such as HLA-A*02:01) in the HLA typing.

Related topics

HLA and autoimmunityEBV sequence tracesHLA typing

Sources

  1. 1International MS Genetics Consortium, 2019 Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility. Science 365:eaav7188. doi.org/10.1126/science.aav7188
  2. 2Bjornevik et al., 2022 Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis. Science 375:296–301. doi.org/10.1126/science.abj8222
  3. 3Wang et al., 2026 EBV infection and HLA-DR15 jointly drive multiple sclerosis by myelin peptide presentation. Cell 189:569-584. doi.org/10.1016/j.cell.2025.12.046