STRUCTURE OF THE TCR EXPRESSED ON A GASTRITOGENIC T-CELL CLONE, II-6,AND FREQUENT APPEARANCE OF SIMILAR CLONOTYPES IN MICE BEARING AUTOIMMUNE GASTRITIS

A parietal cell-specific T(h)1 clone, IL-6, which was established from a BALB/c mouse bearing post-thymectomy autoimmune gastritis (AIG), re cognizes a peptide of the alpha subunit (alpha(891-905)) of H+/K+- ATP ase and induces gastritis in nu/nu BALB/c mice by adoptive cell transf er. In the present study, the primary structure of the TCR of IL-6 was determined as V(alpha)10-J(alpha)c5a-C-alpha and V(beta)14-J(beta)2.3 -C(beta)2 by cDNA cloning. Using PCR with specific primers, we defined the use of this IL-6 TCR in nu/nu mice with transferred IL-6 cells an d in mice that spontaneously developed AIG by thymectomy on day 3 afte r birth (d3-Tx), IL-6 TCR mRNAs were detected in the gastric mucosa of all of the nu/nu mice, suggesting that IL-6 cells indeed home to the gastric mucosa and thereby were directly involved in the destruction o f target parietal cells. TCR beta chain mRNAs encoding CDR3 region seq uences almost identical with that of IL-6 were also found in the gastr ic mucosa in 43% (six of 14 mice tested) of the d3-Tx AIG mice at 4-12 weeks old by nested RT-PCR. Such a frequent appearance of similar clo notypes in independent individuals suggests that T cells bearing IL-6- like TCR including the IL-6 itself might be directly involved in, alth ough not essential for, the pathogenesis of AIG in 3d-Tx mice.