HLA & immunogenetics

Multiple sclerosis

HLA-DRB1*15:01

Multiple sclerosis is an inflammatory disease of the central nervous system with many genetic and non-genetic influences. HLA-DRB1*15:01 is among its most important genetic risk alleles. Prior Epstein-Barr virus infection is strongly associated with MS; how it interacts with other factors continues to be studied.

Key points

  • DRB1*15:01 raises relative risk in many studies; most carriers do not develop MS.
  • HLA-A*02:01 has been associated with lower risk in several studies.
  • Prior EBV infection precedes most MS cases, but is not a complete explanation on its own.
  • A 2026 study examined how EBV and HLA-DR15 may affect myelin peptide presentation.
WHERE IS THE MYELIN PEPTIDE (MBP) SHOWN ON HLA-DR15?SITEMBP ON HLA-DR15EBV-infected B cellpresentedMS brain tissuethe same peptideHealthy B cellabsentThymusabsentBecause 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 is associated with higher relative MS risk, but does not determine whether the disease develops. In a large longitudinal study, EBV infection preceded almost all observed MS cases; this supports a strong association but does not by itself establish a complete disease mechanism. Proposed mechanisms include molecular mimicry and changes in infected B cells.

How virus and gene act together

An experimental study published in 2026 examined a possible link between EBV infection and HLA-DR15. In the cell and tissue samples studied, the researchers found evidence that infected B cells present myelin basic protein (MBP) peptides and that matching CD4 T cells can respond to them. This offers a possible mechanism, but does not prove that this process alone causes MS or applies in the same way to every patient.

Context

DRB1*15:01 is a risk marker, not a prediction for an individual. HLA typing does not diagnose MS or explain an individual's course or cause. Genome presents the type as technical evidence.

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