Do we think that the gene products of a baby are going to be the same as an adult? Therefore it would not be surprising if EBV influneces what genes are active because one thing it does is…..change the B cell from having the features and coat of a naive B cell to become a memory B cell which has a different coat and different functional capabilities. Memory B cells are good antigen presenting cells and they express HLA-DR the DR15.01 variant is associated with an increased risk of MS. DR15.01 on naive B cells aid the degree of infection of B cells by EBV, so is HLA_DR15*01 likely that it is influenced. It is also well known that myelin basis proteins were associated with HLA-DR15*01 as there did trials of myelin peptides that were changed to generate an antibody helping state from a macrophage helping state…Shame they did the trial in some people who did not express HLA-DR15*01 and the trials failed. They say “The HLA-DR15 molecules DRA01:01/DRB501:01 (DR2a) and DRA01:01/DRB115:01 (DR2b) present peptides to T cell receptors (TCRs) to activate CD4 + T cells, which is consistent with the fact that MS is a CD4 + T cell-mediated autoimmune disease”.
Here they got cells from people with MS and they removed the antigenic peptides (the targets for the immune response) from the MHC and low and behold they did not report detection of glialcam or anocatamin-2 but peptides of myelin basic protein. This a blast from the past but with no mention of the other ones it makes you wonder what is the reality. Alpha B crystallin induced responses barely above background. They find MBP reactive T cells in the blood and CNS of people with MS.
“While still preliminary, immunohistochemical studies of MS brain tissue samples showed positive staining for the EBV latent proteins EBNA2, LMP1…consistent with a recent study (Laderach et al. Nature 2025; 646, 171. 24) so remember recent paper by Kim et al. on CD40 signalling.
Highlights
• EBV infection alters the transcriptome and immunopeptidome of B cells
• EBV-infected B cells present MBP peptides on surface HLADR15 molecules
• MBP peptides on EBV-infected B cells are also presented on HLA-DR15 in MS brain tissue
• MBP peptide-reactive memory CD4 + T cells exist in the periphery and CSF of MS patients
Epstein-Barr virus (EBV) is involved in causing and probably also in perpetuating multiple sclerosis (MS). Among several mechanisms of how EBV may contribute are transcriptome alterations, including changes of antigen processing and preferential presentation of both viral and self-antigens. Here, we report that EBV reprograms the transcriptome and immunopeptidome presented on the MS-associated human leukocyte antigen (HLA)-DR15 molecules of infected B cells. Identical myelin basic protein (MBP) peptides were found to be presented on both EBV-infected B cells and MS brain tissue but not primary B cells and thymic tissue. Peripheral memory and cerebrospinal fluid (CSF)-derived CD4+ T cells of HLA-DR15+ MS patients responded to MBP peptides, MBP(78–90) and/or MBP(83–90), and T cell clones raised with these peptides recognized all MBP peptides ending at amino acid MBP90 in MS brain tissue. Our study provides a new mechanistic link for how the environmental and genetic risk factors, EBV infection and HLA-DR15 haplotype, may contribute jointly to MS.
Source: multiple-sclerosis-research.org