The picture gets more complex: ANO2 + GlialCam + CRYAB
Posted: Fri May 19, 2023 9:49 am
EBNA1 is a EBV protein with several interesting segments: Some of them mimic the human proteins ANO2, GlialCam or CRYAB. Maybe other segments mimic other proteins.
Cross-reactive EBNA1 immunity targets alpha-crystallin B and is associated with multiple sclerosis
https://www.science.org/doi/full/10.1126/sciadv.adg3032
Excerpt:
"One study demonstrated cross-reactivity between EBNA1 amino acids 394 to 399 and GlialCAM (18), and we have previously demonstrated the same for EBNA1 amino acids 431 to 440 with ANO2 (17).
In addition, EBNA1 amino acids 411 to 426 and myelin basic protein cross-reactivity has been demonstrated in experimental autoimmune encephalomyelitis (EAE) (36), and EBNA1-specific T cells have been shown to react to a mixed myelin antigen pool (33).
We now demonstrate further cross-reactivity between EBNA1 amino acids 402 to 406 and CRYAB amino acids 11 to 15, with core sequence homology mapped to identical RRPFF residues within these fragments.
While many proteins contain this core amino acid RRPFF motif, amino acid residues that flank this sequence and are unique to CRYAB are also necessary for antibody binding. This is evidenced by the drop in signal after CRYAB amino acids 8 to 22, indicating that the shared proline at CRYAB position 8 (and at EBNA1 position 399) is critical to the epitope
Several different autoantigens may be involved in mimicry between MS and EBV, which could explain why each study to date has found autoreactivities in only ~20% of pwMS, despite essentially ubiquitous EBNA1 responses. In support of this, we saw a poor correlation between CRYAB and ANO2 IgG responses despite the shared EBNA1 link, which suggests that underlying factors such as human leukocyte antigen (HLA), previous antigen experience of the immune system, history of IM, or other perhaps undiscovered risk factors affect the different cross-reactivity patterns"
Cross-reactive EBNA1 immunity targets alpha-crystallin B and is associated with multiple sclerosis
https://www.science.org/doi/full/10.1126/sciadv.adg3032
Excerpt:
"One study demonstrated cross-reactivity between EBNA1 amino acids 394 to 399 and GlialCAM (18), and we have previously demonstrated the same for EBNA1 amino acids 431 to 440 with ANO2 (17).
In addition, EBNA1 amino acids 411 to 426 and myelin basic protein cross-reactivity has been demonstrated in experimental autoimmune encephalomyelitis (EAE) (36), and EBNA1-specific T cells have been shown to react to a mixed myelin antigen pool (33).
We now demonstrate further cross-reactivity between EBNA1 amino acids 402 to 406 and CRYAB amino acids 11 to 15, with core sequence homology mapped to identical RRPFF residues within these fragments.
While many proteins contain this core amino acid RRPFF motif, amino acid residues that flank this sequence and are unique to CRYAB are also necessary for antibody binding. This is evidenced by the drop in signal after CRYAB amino acids 8 to 22, indicating that the shared proline at CRYAB position 8 (and at EBNA1 position 399) is critical to the epitope
Several different autoantigens may be involved in mimicry between MS and EBV, which could explain why each study to date has found autoreactivities in only ~20% of pwMS, despite essentially ubiquitous EBNA1 responses. In support of this, we saw a poor correlation between CRYAB and ANO2 IgG responses despite the shared EBNA1 link, which suggests that underlying factors such as human leukocyte antigen (HLA), previous antigen experience of the immune system, history of IM, or other perhaps undiscovered risk factors affect the different cross-reactivity patterns"