T cell antigen receptor expression in athymic (nu/nu) mice. Evidence for an oligoclonal beta chain repertoire

Abstract

The expression of T cell antigen receptors (TCR) in congenitally athymic (nude) mice has been investigated. Lymph node T cells from 4-5-mo-old athymic mice expressed full-length transcripts for the TCR alpha and beta chains at a level two-to three-fold lower than normal littermate (nu/+) controls. Low levels of expression of TCR protein at the surface of a proportion of nude T cells was demonstrated by staining with monoclonal antibodies KJ16-133 and F23.1 (directed against protein products of a family of TCR beta chain variable region genes known as V beta 8). Immunoprecipitation studies confirmed that F23.1 reacted with a similar molecular species on nude and nu/+ T cells. Studies with individual nude mice revealed a striking heterogeneity in the proportion of T cells expressing KJ16/F23.1 that was not seen in normal animals. This heterogeneity correlated with the expression of mRNA specific for V beta 8 but not with total expression of full-length beta chain transcripts. Analysis of Lyt-2+ and L3T4+ T cell subsets in individual nude mice further demonstrated that F23.1 expression was frequently associated with only one subset, and several cases were seen in which all L3T4+ cells expressed F23.1. In contrast, a similar (and constant) proportion of Lyt-2+ or L3T4+ T cells expressed F23.1 in control mice. Southern blotting of Hind III-digested DNA from nude T cells with a C beta probe revealed a more restricted pattern of TCR beta chain rearrangements than was seen for normal T cells. Taken together, these data provide compelling evidence that TCR gene rearrangement and expression can occur extrathymically. Furthermore, they suggest a model according to which the restricted functional repertoire of T cells previously observed in individual nude mice results from an oligoclonal expansion of T cells that have randomly rearranged and expressed TCR beta chain genes.