T-CELLS FROM THE SMALL-INTESTINAL MUCOSA OF A DR4,DQ7 DR4,DQ8 CELIAC-DISEASE PATIENT PREFERENTIALLY RECOGNIZE GLIADIN WHEN PRESENTED BY DQ8

CD is an immunologic disease of the small intestine which is precipita ted by ingestion of wheat gliadin. Most patients carry the HLA-DQ (alp ha 1()0501,beta 1(*)0201) (DQ2) heterodimer. We recently reported tha t a preponderance of gliadin-specific T cells from the small intestina l mucosa of DQ2-positive CD patients were restricted by this DQ hetero dimer. However, a small percentage of CD patients do not carry this DQ heterodimer, and most of them instead carry DQ (alpha 1()0301,beta 1 ()0302) (DQ8). Here we report that a majority of gliadin-specific T c ells from the small intestinal mucosa of a DR4,DQ7/DR4,DQ8 heterozygou s CD patient are restricted by DQ8. Thus, preferential presentation of gliadin-derived peptides to T cells by the CD-associated DQ2 and DQ8 molecules may be an initial and important immunopathogenic step in CD.