Defining T cell receptors which recognise the immunodominant epitope of the gastric autoantigen, the H/K ATPase beta-subunit

We have previously shown that autoimmune gastritis can be elicited in mice by immunisation with the gastric parietal cell H/K ATPase alpha beta hetero dimer, and, furthermore, have identified the H/K ATPase beta -subunit epito pe, H/K beta (253-277) as the dominant epitope of the gastric H/K ATPase. U sing gastric H/K ATPase-immunised mice, here we have generated two T cell h ybridomas specific for the H/K beta (253-277) peptide, namely 4B11.F4.5 and 1E4.C1. Hybridoma 4B11.F4.5 uses V alpha8 and V beta8.2 TCR chains and 1E4 .C1 uses V alpha9 and V beta8.3 chains. Although both hybridomas are specif ic for H/K beta (253-277) T cell assays using overlapping 14-mers of the 25 -mer epitope showed that the two autoreactive TCRs recognise different regi ons of the 25-mer. The TCR from 1E4.C1 has been used to generate a TCR beta -chain transgenic mouse. >80% of peripheral CD4(+) T cells utilise the V b eta8.3 transgene. As expected, 1E4-TCR beta -chain transgenic mice are susc eptible to neonatal thymectomy induced autoimmune gastritis. While none of the 1E4-TCR beta chain transgenic mice spontaneously developed a destructiv e gastritis, a minority (20%) of the transgenic mice developed a non-invasi ve and non-destructive gastritis. This suggests that the pathogenic T cells are maintained in a tolerant state in the periphery of the transgenic mice .