The HLA-DR2 haplotype is associated with an increased proliferative response to the immunodominant CD4(+) T-cell epitope in human interferon-beta.
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.
Stickler
M
M
Genencor International, Palo Alto, CA 94304, USA.
Valdes
A M
AM
Gebel
W
W
Razo
O J
OJ
Faravashi
N
N
Chin
R
R
Rochanayon
N
N
Harding
F A
FA
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006683:HLA-DQ Antigens / Q000276:immunology; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology*; D006239:Haplotypes / Q000276:immunology; D006801:Humans; D016899:Interferon-beta / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D009103:Multiple Sclerosis / Q000209:etiology / Q000276:immunology; D004676:Myelin Basic Protein / Q000276:immunology; D011110:Polymorphism, Genetic / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D004676:Myelin Basic Protein; D016899:Interferon-beta