T cells recognize a peptide derived from alpha-gliadin presented by the celiac disease-associated HLA-DQ (alpha 1*0501, beta 1*0201) heterodimer.
CD is unique among the HLA-associated diseases since (a) the disease-promoting agent (gliadin) is known and (b) the disease is precipitated mainly in individuals carrying a particular cis- or trans-encoded HLA-DQ heterodimer; i.e., DQ(alpha 1*0501, beta 1*0201). Further, a preponderance of gliadin-specific T cells derived from the small intestinal mucosa of CD patients are restricted by this DQ heterodimer. T-cell recognition of gliadin peptides presented by the DQ(alpha 1*0501, beta 1*0201) heterodimer may thus be of importance in CD. Here we report that a T-cell clone from a patient with CD recognizes a synthetic alpha-gliadin peptide, when presented by the cis- or trans-encoded CD-associated DQ(alpha 1*0501, beta 1*0201) heterodimer. The minimal peptide recognized by the T-cell clone corresponds to residues 31-47 of alpha-gliadin, which is included in the part of alpha-gliadin previously shown to have disease-promoting activity. When testing analogue peptides derived from other alpha-gliadin sequences, one peptide differing by one amino acid was recognized by the T-cell clone, whereas the other peptide differing by two amino acids was not recognized. Our findings demonstrate that the CD-associated DQ(alpha 1*0501, beta 1*0201) heterodimer may serve as an antigen-presenting molecule to T cells for certain gliadin peptides.
Gjertsen
H A
HA
Institute of Transplantation Immunology, National Hospital, Oslo, Norway.
Lundin
K E
KE
Sollid
L M
LM
Eriksen
J A
JA
Thorsby
E
E
D000595:Amino Acid Sequence; D017951:Antigen Presentation / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology; D002446:Celiac Disease / Q000276:immunology*; D002460:Cell Line; D002478:Cells, Cultured; D002999:Clone Cells; D000939:Epitopes / Q000276:immunology; D005260:Female; D005903:Gliadin / Q000138:chemical synthesis / Q000276:immunology*; D006683:HLA-DQ Antigens / Q000235:genetics / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000939:Epitopes; D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; D010455:Peptides; D005903:Gliadin