Genes Immun. 2004 Jan;5(1):1-7
Stickler M, Valdes AM, Gebel W, Razo OJ, Faravashi N, Chin R, Rochanayon N, Harding FA.
Genencor International, Palo Alto, CA, USA.
Human CD4+ T-cell epitopes were identified in interferon-beta (IFN-beta)-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-beta 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-beta and MS might explain the prevalence of neutralizing antibody development, and may underlie the etiology of the disease.