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 alphabeta heterodimer, and, furthermore, have identified the H/K ATPase beta-subunit epitope, H/Kbeta253-277 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/Kbeta253-277 peptide, namely 4B11.F4.5 and 1E4.C1. Hybridoma 4B11.F4.5 uses Valpha8 and Vbeta8.2 TCR chains and 1E4.C1 uses Valpha9 and V1beta8.3 chains. Although both hybridomas are specific for H/Kbeta253-277, 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 beta-chain transgenic mouse. >80% of peripheral CD4+ T cells utilise the Vbeta8.3 transgene. As expected, 1E4-TCR beta-chain transgenic mice are susceptible to neonatal thymectomy induced autoimmune gastritis. While none of the 1E4-TCR beta 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.
De Silva
H D
HD
Department of Pathology and Immunology Monash University Medical School, Melbourne, Victoria, Austrialia.
Alderuccio
F
F
Toh
B H
BH
van Driel
I R
IR
Gleeso
P A
PA
D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D001483:Base Sequence; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D017506:H(+)-K(+)-Exchanging ATPase / Q000276:immunology*; D006825:Hybridomas; D016056:Immunodominant Epitopes / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*; D013270:Stomach / Q000201:enzymology* / Q000276:immunology
D001324:Autoantigens; D018984:Epitopes, T-Lymphocyte; D016056:Immunodominant Epitopes; D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta; D017506:H(+)-K(+)-Exchanging ATPase