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HLA-DRB1*1501 risk association in multiple sclerosis may not be related to presentation of myelin epitopes.
J Neurosci Res 2004; 78(1):100-14JN

Abstract

Susceptibility to multiple sclerosis (MS) is associated genetically with human leucocyte antigen (HLA) class II alleles, including DRB1*1501, DRB5*0101, and DQB1*0602, and it is possible that these alleles contribute to MS through an enhanced ability to present encephalitogenic myelin peptides to pathogenic T cells. HLA-DRB1*1502, which contains glycine instead of valine at position 86 of the P1 peptide-binding pocket, is apparently not genetically associated with MS. To identify possible differences between these alleles in their antigen-presenting function, we determined if T-cell responses to known DRB1*1501-restricted myelin peptides might be diminished or absent in transgenic (Tg) DRB1*1502-expressing mice. We found that Tg DRB1*1502 mice had moderate to strong T-cell responses to several myelin peptides with favorable DRB1*1501 binding motifs, notably myelin oligodendrocyte glycoprotein (MOG)-35-55 (which was also encephalitogenic), proteolipid protein (PLP)-95-116, and MOG-194-208, as well as other PLP and MOG peptides. These peptides, with the exception of MOG-194-208, were also immunogenic in healthy human donors expressing either DRB1*1502 or DRB1*1501. In contrast, the DRB1*1502 mice had weak or absent responses to peptides with unfavorable DRB1*1501 binding motifs. Overall, none of the DRB1*1501-restricted myelin peptides tested selectively lacked immunogenicity in association with DRB1*1502. These results indicate that the difference in risk association with MS of DRB1*1501 versus DRB1*1502 is not due to a lack of antigen presentation by DRB1*1502, at least for this set of myelin peptides, and suggest that other mechanisms involving DRB1*1501 may account for increased susceptibility to MS.

Authors+Show Affiliations

Neuroimmunology Research, Veterans Affairs Medical Center, Portland, Oregon 97239, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15372502

Citation

Finn, Thomas P., et al. "HLA-DRB1*1501 Risk Association in Multiple Sclerosis May Not Be Related to Presentation of Myelin Epitopes." Journal of Neuroscience Research, vol. 78, no. 1, 2004, pp. 100-14.
Finn TP, Jones RE, Rich C, et al. HLA-DRB1*1501 risk association in multiple sclerosis may not be related to presentation of myelin epitopes. J Neurosci Res. 2004;78(1):100-14.
Finn, T. P., Jones, R. E., Rich, C., Dahan, R., Link, J., David, C. S., ... Vandenbark, A. A. (2004). HLA-DRB1*1501 risk association in multiple sclerosis may not be related to presentation of myelin epitopes. Journal of Neuroscience Research, 78(1), pp. 100-14.
Finn TP, et al. HLA-DRB1*1501 Risk Association in Multiple Sclerosis May Not Be Related to Presentation of Myelin Epitopes. J Neurosci Res. 2004 Oct 1;78(1):100-14. PubMed PMID: 15372502.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - HLA-DRB1*1501 risk association in multiple sclerosis may not be related to presentation of myelin epitopes. AU - Finn,Thomas P, AU - Jones,Richard E, AU - Rich,Cathleen, AU - Dahan,Rony, AU - Link,Jason, AU - David,Chella S, AU - Chou,Yuan K, AU - Offner,Halina, AU - Vandenbark,Arthur A, PY - 2004/9/17/pubmed PY - 2005/2/8/medline PY - 2004/9/17/entrez SP - 100 EP - 14 JF - Journal of neuroscience research JO - J. Neurosci. Res. VL - 78 IS - 1 N2 - Susceptibility to multiple sclerosis (MS) is associated genetically with human leucocyte antigen (HLA) class II alleles, including DRB1*1501, DRB5*0101, and DQB1*0602, and it is possible that these alleles contribute to MS through an enhanced ability to present encephalitogenic myelin peptides to pathogenic T cells. HLA-DRB1*1502, which contains glycine instead of valine at position 86 of the P1 peptide-binding pocket, is apparently not genetically associated with MS. To identify possible differences between these alleles in their antigen-presenting function, we determined if T-cell responses to known DRB1*1501-restricted myelin peptides might be diminished or absent in transgenic (Tg) DRB1*1502-expressing mice. We found that Tg DRB1*1502 mice had moderate to strong T-cell responses to several myelin peptides with favorable DRB1*1501 binding motifs, notably myelin oligodendrocyte glycoprotein (MOG)-35-55 (which was also encephalitogenic), proteolipid protein (PLP)-95-116, and MOG-194-208, as well as other PLP and MOG peptides. These peptides, with the exception of MOG-194-208, were also immunogenic in healthy human donors expressing either DRB1*1502 or DRB1*1501. In contrast, the DRB1*1502 mice had weak or absent responses to peptides with unfavorable DRB1*1501 binding motifs. Overall, none of the DRB1*1501-restricted myelin peptides tested selectively lacked immunogenicity in association with DRB1*1502. These results indicate that the difference in risk association with MS of DRB1*1501 versus DRB1*1502 is not due to a lack of antigen presentation by DRB1*1502, at least for this set of myelin peptides, and suggest that other mechanisms involving DRB1*1501 may account for increased susceptibility to MS. SN - 0360-4012 UR - https://www.unboundmedicine.com/medline/citation/15372502/HLA_DRB1_1501_risk_association_in_multiple_sclerosis_may_not_be_related_to_presentation_of_myelin_epitopes_ L2 - https://doi.org/10.1002/jnr.20227 DB - PRIME DP - Unbound Medicine ER -