HLA restriction patterns of gliadin- and astrovirus-specific CD4(+) T cells isolated in parallel from the small intestine of celiac disease patients

Celiac disease is a common HLA-DQ2-associated enteropathy caused by an abno rmal T-cell-mediated immune response to ingested wheat gliadin proteins. We have previously isolated in situ activated mucosal T cells from celiac dis ease patients and demonstrated that these T cells were gliadin specific and predominantly DQ2 restricted. In contrast to this, gliadin-specific T cell s isolated from peripheral blood display a variable HLA restriction pattern , thereby indicating that the skewed DQ restriction of T cells resident in the celiac lesions could be dictated by a preference for DQ-mediated antige n presentation in the mucosa of CD patients. To address this, we analyzed t he HLA restriction of T cells recognizing astrovirus, a common gastroenteti tis virus, isolated from intestinal mucosa of six celiac disease patients. As an internal control, gliadin-specific T cells were isolated and analyzed in parallel. The gliadin-specific mucosal T cells were marked in their DQ2 restriction, whereas the parallel astrovirus-specific T cells were predomi nantly restricted by DR molecules, Our data indicate that the repertoire of T cells present in celiac lesions is determined by the priming antigen(s) and not by a skewing in the expression of functional HLA class II isotypes in the disease affected small intestinal mucosa.