Diminished Expression of the T Cell Receptor on the Expanded Lymphocyte Population in Mrl/Mp-1pr/1pr Mice

Abstract

MRL mice homozygous for the recessive 1pr gene develop an accelerated autoimmune syndrome and massive lymphadenopathy. Because the function of the expanded lymph node population is unclear, we have studied the subunits of the T cell receptor for antigen (TcR). DNA and RNA were prepared from MRL/Mp-1pr/1pr (1pr) and congenic MRL/Mp- +/+ (+/+) mice by standard techniques and studied by Southern blot, northern blot, and dot blot analysis using the cDNAs TT11, specific for the TcR α chain; 86T5, specific for the TcR β chain; and T3δ; specific for the subunit of the T3 molecule. Surface protein was immunoprecipitated with antisera 8177, which recognizes TcR framework determinants, and resolved by diagonal SDS-PAGE. FACS analysis was performed with a monoclonal antibody to murine T3, and with the KJ16-133 and F23.1 monoclonal antibodies, which recognize determinants encoded by the Vβ8 subfamily of β chain variable region genes.

When compared with +/+ controls, surface TcR density as detected by immunofluorescence using all three antibodies was significantly diminished on 1pr spleen and lymph node cells, as well as on 1pr lymph node cells which had been depleted of L3T4⁺ and Ly2⁺ cells by negative selection. There appeared, however, to be selective expression of the genes encoding the epitopes binding F23.1. Southern blot analysis of DNA showed polyclonal rearrangements of the TcR β chain genes. There were increased α, β, and T3δ RNA transcripts in the double negative lymph node cells. The paradoxical decrease in TcR surface expression in the setting of large quantities of full length transcript is yet to be explained.

Key Words:

• Systemic lupus erythematosus
• murine models
• T cell receptor
• autoimmune disease