HLA-DR53 molecules are associated with susceptibility to celiac disease and selectively bind gliadin-derived peptides.
Celiac disease (CD) patients usually express a DQ2 heterodimer, whose chains DQalpha1*0501/DQbeta1*0201, are encoded by the genes HLA-DQA1*0501 and DQB1*0201, respectively. Among the DQ2 carriers, the risk of developing disease was shown to correlate with the number of DQbeta1*0201 chains encoded. Studying two separate cohorts of Italian and Tunisian patients, we now show a significant association of celiac disease with expression of either the DQ2 or DR53 heterodimers. The risk is maximal for individuals that carry both DQ2 and DR53 heterodimers. When twenty synthetic peptides overlapping most of A-gliadin sequence were tested for the binding to various purified DR molecules, it was found that DR53 molecules bind selectively and with high affinity (IC50<1 microM) to A-gliadin-derived peptides. These data suggest that both HLA DQ2 and DR53 molecules are associated with increased genetic risk for CD, and provide a possible biochemical basis for this complex association.
Laboratoire de Génétique Moléculaire Humaine, Université de Versailles, 25 avenue des Etats-Unis, 78000 Versailles, France.
F
F
Clot
C
C
Gianfrani
M C
MC
Babron
F
F
Bouguerra
S
S
Southwood
M F
MF
Kagnoff
R
R
Troncone
S
S
Percopo
J F
JF
Eliaou
F
F
Clerget-Darpoux
A
A
Sette
L
L
Greco
D001667:Binding, Competitive; D002446:Celiac Disease / Q000235:genetics*; D015331:Cohort Studies; D019281:Dimerization; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005903:Gliadin / Q000378:metabolism*; D006683:HLA-DQ Antigens / Q000235:genetics; D006684:HLA-DR Antigens / Q000737:chemistry / Q000235:genetics* / Q000302:isolation & purification; D059845:HLA-DRB4 Chains; D006801:Humans; D007558:Italy; D011485:Protein Binding; D012307:Risk Factors; D014416:Tunisia
D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; C050610:HLA-DR53; D059845:HLA-DRB4 Chains; D005903:Gliadin