Loading Rate of Exogenous and Autoantigenic Determinants on Major Histocompatibility Complex Class II Mediates Resistance to Multiple Sclerosis
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Genetic analysis of thousands of patients with multiple sclerosis (MS) and healthy Russian donors showed that the carriage of groups of HLA-DRB1*15 and HLA-DRB1*03 alleles is associated with the risk of MS, whereas the carriage of groups of HLA-DRB1*01 and HLA-DRB1*11 alleles is protective. Recombinant HLA-DRB1*01:01 with a high affinity can recognize the fragments of myelin basic protein (MBP), one of the autoantigens in MS. However, the comparison of the kinetic parameters of the load of MBP and viral HA peptides on HLA-DRB1*01:01, which is catalyzed by HLA-DM, showed a significantly lower rate of exchange of CLIP for MBP peptides. We assume that the observed protective properties of the group of HLA-DRB1*01 alleles may be directly associated with the ability of HLA-DRB1*01:01 to kinetically distinguish peptides of exogenous and endogenous nature.
- 1.Sudomoina, M.A., Boiko, A.N., Demina, T.L., Gusev, E.I., Boldyreva, M.N., Trofimov, D.Y., Alekseev, L.P., and Favorova, O.O., Association of multiple sclerosis in the Russian population with HLA-DRB1 gene alleles, Mol Biol., 1998, vol. 32, pp. 291–296Google Scholar
- 4.Belogurov, A.A., Kurkova, I.N., Friboulet, A., Thomas, D., Misikov, V.K., Zakharova, M.Y., Suchkov, S.V., Kotov, S.V., Alehin, A.I., Avalle, B., et al., Recognition and degradation of myelin basic protein peptides by serum autoantibodies: novel biomarker for multiple sclerosis, J. Immunol., 2008, vol. 180, pp. 1258–1267. https://doi.org/10.4049/jimmunol.180.2.1258 CrossRefGoogle Scholar
- 6.Anders, A.K., Call, M.J., Schulze, M.S.E.D., Fow-ler, K.D., Schubert, D.A., Seth, N.P., Sundberg, E.J., and Wucherpfennig, K.W., HLA-DM captures partially empty HLA-DR molecules for catalyzed removal of peptide, Nat. Immunol., 2011, vol. 12, pp. 54–61. https://doi.org/10.1038/ni.1967 CrossRefGoogle Scholar