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Critical residues on HLA-DRB1*0402 HV3 peptide for HLA-DQ8-restricted immunogenicity: implications for rheumatoid arthritis predisposition.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 1997 Apr 01; Vol. 158 (7), pp. 3545-51. - Publication Year :
- 1997
-
Abstract
- Recently, we have proposed that the combination of HLA-DQ and -DR alleles is responsible for the association of the HLA class II region with rheumatoid arthritis (RA). According to this model, some HLA-DQ alleles, namely DQ4, DQ7, DQ8, and DQ9, predispose carriers to severe RA, but a self peptide of sequence KDILEDERAAVDTYC from the third hypervariable (HV3) region of some DRB1 alleles, including DRB1*0402, can protect from the disease if presented by DQ molecules. This model implies that DQ4, DQ7, DQ8, and DQ9 should be able to present a set of common peptides, despite polymorphisms in their Ag binding groove. In the present study, we have further analyzed the immunogenicity of the DRB1*0402 HV3 peptide in DQ8-transgenic mice. We found that the motif DERAA guarantees DQ8-restricted immunogenicity, and that R is the main anchor residue for binding of the DRB1*0402 peptide to DQ. Interestingly, the p1 pocket that probably controls binding of the R residue is identical in all four RA-associated DQ molecules. Our results imply that the association of RA with some DR subtypes can be explained by their linkage with DQ alleles displaying a binding site for similar "arthritogenic" peptides.
- Subjects :
- Amino Acid Sequence
Animals
Arthritis, Rheumatoid genetics
Disease Susceptibility
HLA-DQ Antigens genetics
HLA-DRB1 Chains
Immunodominant Epitopes immunology
Mice
Mice, Transgenic
Molecular Sequence Data
Arthritis, Rheumatoid immunology
HLA-DQ Antigens immunology
HLA-DR Antigens chemistry
HLA-DR Antigens immunology
Peptide Fragments immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 158
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 9120317