Defining T Cell Receptors which Recognise the Immunodominant Epitope of the Gastric Autoantigen, the H/K ATPase β-Subunit

• Published in: Autoimmunity (Chur, Switzerland) Vol. 33; no. 1; pp. 1 - 14
• Main Authors: De Silva, Harini D., Alderuccio, Frank, Toh, Ban Hock, Van Driel, Ian R., GleesOn, Paul A.
• Format: Journal Article
• Language: English
• Published: Abingdon Informa UK Ltd 01-01-2001; Taylor & Francis; Taylor and Francis
• Subjects: Amino Acid Sequence; Animals; Autoantigens - immunology; autoimmune gastritis; autoimmunity; Base Sequence; Biological and medical sciences; Epitope Mapping; Epitopes, T-Lymphocyte - immunology; Experimental and animal immunopathology. Animal models; Female; H(+)-K(+)-Exchanging ATPase - immunology; H/K ATPase; Hybridomas; Immunodominant Epitopes - immunology; Immunopathology; Male; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Transgenic; Molecular Sequence Data; Peptides - immunology; Receptors, Antigen, T-Cell, alpha-beta - genetics; Receptors, Antigen, T-Cell, alpha-beta - immunology; Stomach - enzymology; Stomach - immunology; T-cell epitope; Autoimmunity; Animal model; Antigenic determinant; Pathogenesis; Beta-Peptide chain; Transgenic animal; H; Helper cell; Autoimmune disease; Hemopathy; B-Vitamins; K; Biermer disease; T-Lymphocyte; Gastric disease; Immunopathology; Stomach; T cell receptor; Immune response; Enzyme; Rodentia; Nutrition disorder; Vitamin deficiency; Cell subpopulation; Gastritis; Vertebrata; Mammalia; Autoantigen; Mouse; Animal; Digestive diseases; Hydrolases; Alpha-Peptide chain; exchanging ATPase
• ISSN: 0891-6934; 1607-842X
• DOI: 10.3109/08916930108994104

We have previously shown that autoimmune gastritis can be elicited in mice by immunisation with the gastric parietal cell H/K ATPase αβ heterodimer, and, furthermore, have identified the H/K ATPase β-subunit epitope, H/Kβ253-277 as the dominant epitope of the gastric H/K ATPase. Using gastric H/K ATPase-immunised mice, here we have generated two T cell hybridomas specific for the H/Kβ253-277 peptide, namely 4B11.F4.5 and 1E4.C1. Hybridoma 4B11.F4.5 uses Vα8 and Vp8.2 TCR chains and 1E4.C1 uses Vα9 and Vβ8.3 chains. Although both hybridomas are specific for H/Kβ253-277. T cell assays using overlapping 14-mers of the 25-mer epitope showed that the two autoreactive TCRs recognise different regions of the 25-mer. The TCR from 1E4.C1 has been used to generate a TCR β-chain transgenic mouse. $80% of peripheral CD4+ T cells utilise the Vβ8.3 transgene. As expected, 1E4-TCR (3-chain transgenic mice are susceptible to neonatal thymectomy induced autoimmune gastritis. While none of the 1E4-TCR β chain transgenic mice spontaneously developed a destructive gastritis, a minority (20%) of the transgenic mice developed a non-invasive and non-destructive gastritis. This suggests that the pathogenic T cells are maintained in a tolerant state in the periphery of the transgenic mice