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The HLA-DR2 haplotype is associated with an increased proliferative response to the immunodominant CD4+ T-cell epitope in human interferon-β

Genes & Immunity volume 5, pages 1–7 (2004)Cite this article

Abstract

Human CD4+ T-cell epitopes were identified in interferon-beta (IFN-β)-1b. A prominent peptide epitope region was found that induced a proliferative response in 16% of all donors tested. Responses corresponded to the presence of the HLA-DR2 haplotype. Responsive donors expressing the HLA-DQ6 allele showed an increased level of proliferation to the epitope as compared to peptide-responsive HLA-DQ6 negative donors. A similar result was found for HLA-DR15-expressing donors. PBMC from donors expressing HLA-DR15 were more likely to proliferate in response to IFN-β in a whole-protein in vitro assay than donors who did not carry this haplotype. It is striking that the common DQ6 allele HLA-DQB1*0602 is found in linkage disequilibrium with HLA-DRB1*1501, and this combination defines the HLA genotype associated with the development of multiple sclerosis. The HLA association between a response to IFN-β and MS might explain the prevalence of neutralizing antibody development, and may underlie the etiology of the disease.

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Acknowledgements

We thank Dr Jorge Oksenberg for his useful discussions and critical reading of the manuscript.

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Authors and Affiliations

  1. Genencor International, Palo Alto, CA, USA

    M Stickler, W Gebel, O J Razo, N Faravashi, R Chin, N Rochanayon & F A Harding

  2. Department of Medicine and Endocrinology, University Campus Bio-Medico, Rome, Italy

    A M Valdes

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  1. M Stickler
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  2. A M Valdes
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  7. N Rochanayon
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  8. F A Harding
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Correspondence to F A Harding.

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Stickler, M., Valdes, A., Gebel, W. et al. The HLA-DR2 haplotype is associated with an increased proliferative response to the immunodominant CD4+ T-cell epitope in human interferon-β. Genes Immun 5, 1–7 (2004). https://doi.org/10.1038/sj.gene.6364027

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