The rheumatoid arthritis-associated allele HLA-DR10 (DRB1*1001) shares part of its repertoire with HLA-DR1 (DRB1*0101) and HLA-DR4 (DRB*0401).
OBJECTIVE
To identify the peptide anchor motif for the rheumatoid arthritis (RA)-related HLA allele, DR10, and find shared natural ligands or sequence similarities with the other disease-associated alleles, DR1 and DR4.


METHODS
The HLA-DR10-associated peptides were purified, and a proportion of these natural ligands were de novo sequenced by mass spectrometry. Based on crystallographic structures, the complexes formed by peptide influenza virus hemagglutinin HA306-318 with DR1, DR4, and DR10 were modeled, and binding scores were obtained.


RESULTS
A total of 238 peptides were sequenced, and the anchor motif of the HLA-DR10 peptide repertoire was defined. A large proportion of the DR10-associated peptides had the structural features to bind DR1 and DR4 but were theoretical nonbinders to the negatively associated alleles DR15 and DR7. Among the sequenced ligands, 10 had been reported as ligands to other RA-associated alleles. Modeling data showed that peptide HA306-318 can bind DR1, DR4, and DR10 with similar affinities.


CONCLUSIONS
The data show the presence of common peptides in the repertoires of RA-associated HLA alleles. The combination of the shared epitope present in DR1, DR4, and DR10 together with common putative arthritogenic peptide(s) could influence disease onset or outcome.
Alvarez
Iñaki
I
Universitat Autònoma de Barcelona, Barcelona, Spain.
Collado
Javier
J
Daura
Xavier
X
Colomé
Nuria
N
Rodríguez-García
Marta
M
Gallart
Teresa
T
Canals
Francesc
F
Jaraquemada
Dolores
D
D000595:Amino Acid Sequence; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D045744:Cell Line, Tumor; D003461:Crystallography; D000939:Epitopes / Q000737:chemistry*; D015234:HLA-A Antigens / Q000737:chemistry*; D006684:HLA-DR Antigens / Q000737:chemistry*; D059810:HLA-DR Serological Subtypes; D015804:HLA-DR4 Antigen / Q000737:chemistry*; D059811:HLA-DRB1 Chains; D006801:Humans; D008024:Ligands; D013058:Mass Spectrometry; D010455:Peptides / Q000737:chemistry
D000939:Epitopes; D015234:HLA-A Antigens; D006684:HLA-DR Antigens; D059810:HLA-DR Serological Subtypes; C421823:HLA-DR10 antigen; D015804:HLA-DR4 Antigen; D059811:HLA-DRB1 Chains; C487961:HLA-DRB1*01:01 antigen; D008024:Ligands; D010455:Peptides