T-CELLS RECOGNIZE A PEPTIDE DERIVED FROM ALPHA-GLIADIN PRESENTED BY THE CELIAC DISEASE-ASSOCIATED HLA-DQ (ALPHA-1-ASTERISK-O5O1, BETA-1-ASTERISK-0201) HETERODIMER

CD is unique among the HLA-associated diseases since (a) the disease-p romoting 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 10501,beta 1*0201). Further, a prepond erance of gliadin-specific T cells derived from the small intestinal m ucosa of CD patients are restricted by this DQ heterodimer. T-cell rec ognition of gliadin peptides presented by the DQ(alpha 10501,beta 1*0 201) 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-gli adin peptide, when presented by the cis- or trans-encoded CD-associate d DQ(alpha 10501,beta 1*0201) heterodimer. The minimal peptide recogn ized by the T-cell clone corresponds to residues 31-47 of alpha-gliadi n, which is included in the part of alpha-gliadin previously shown to have disease-promoting activity. When resting analogue peptides derive d from other alpha-gliadin sequences, one peptide differing by one ami no acid was recognized by the T-cell clone, whereas the other peptide differing by two amino acids was not recognized. Our findings demonstr ate that the CD-associated DQ(alpha 10501,beta 1*0201) heterodimer ma y serve as an antigen-presenting molecule to T cells for certain gliad in peptides.