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), recognizes a peptide of the alpha subunit (alpha(891-905)) of H+/K+- ATPase and induces gastritis in nu/nu BALB/c mice by adoptive cell transfer. 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 and in mice that spontaneously developed AIG by thymectomy on day 3 after 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 of target parietal cells. TCR beta chain mRNAs encoding CDR3 region sequences almost identical with that of IL-6 were also found in the gastric 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 clonotypes in independent individuals suggests that T cells bearing IL-6-like TCR including the IL-6 itself might be directly involved in, although not essential for, the pathogenesis of AIG in 3d-Tx mice.