Restricted T cell receptor repertoire for acetylcholine receptor in murine myasthenia gravis.
Immunization of C57BL/6 mice with AChR provokes symptoms similar to those seen in the disease myasthenia gravis. To elucidate the structural requirements for T cell recognition of AChR and to identify TcR features which might provide targets for immunotherapy, a panel of T cell hybridomas was generated after immunization of mice with the immunodominant peptide of the AChR alpha chain. The TcR genes expressed by these hybridomas were sequenced. TcR-V beta 6 was preferentially employed, but other V beta genes were also observed. A conserved acidic residue was present in all CDR3 regions, regardless of the V beta. The TcR-V alpha repertoire was somewhat skewed with three V alpha families accounting for 82% of the sequences. The utilization of multiple T cell receptor V beta genes may contribute to the inability to inhibit EAMG by elimination of V beta 6+ T cells.
Kraig
E
E
Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio 78284, USA. kraig@uthscsa.edu
Pierce
J L
JL
Clarkin
K Z
KZ
Standifer
N E
NE
Currier
P
P
Wall
K A
KA
Infante
A J
AJ
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006825:Hybridomas; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009157:Myasthenia Gravis / Q000276:immunology*; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry* / Q000235:genetics; D011978:Receptors, Nicotinic / Q000276:immunology*
D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011978:Receptors, Nicotinic