Antigen-specific, I-A-restricted suppressor hybridomas with spontaneous cytolytic activity. Functional properties and lack of rearrangement of the T cell receptor beta chain genes.

Abstract

Since their discovery in 1971 (1, 2), T suppressor (Ts) ~ cells have been the object of numerous studies. Particularly helpful in the characterization of Ts cells was the establishment of cloned T cell lines, such as T cell hybridomas, long-term T cell lines, or transformed T cells (for a survey see 3). A surprisingly large number of Ts subpopulations have been distinguished. Ts and suppressor factors (TsF) derived from them belong either to the inducing arm of the suppressor circuit or to the effector arm that ultimately mediates suppression. They appear to be either antigen specific or nonspecific, H-2 restricted, and heavy chain variable region (VH) restricted or nonrestricted (reviewed in 4-6). Recent advances (7-17) in the molecular and genetic characterization of antigenspecific receptors of T cells, consisting of two chains, a and ~8, have not only revealed some degree of homology to immunoglobulin but also a basic similarity of receptors on T helper cells (Th) and cytotoxic T iymphocytes (Tc). In contrast, the nature of the antigen receptors on Ts remains elusive. The rearrangement of/3 chain genes described for Th and Tc have not been observed in most antigen-specific Ts cells (18), suggesting that the receptor molecule of the Ts cell is unique. However, none of the murine Ts cells that have been investigated for rearrangement were class II or class I major histocompatibility complex (MHC) restricted, as were the Th and Tc lines, respectively.In the present report we describe the establishment and functional characterization of Ts hybridomas that are antigen specific and I-A restricted. In this respect the Ts hybridomas are similar to Th cells.

T-cell clones and T-cell receptors.

“…Similar conclusions were reached in studies with human T-cell clones (189). However, most suppressor T-lymphocyte hybridomas showed no 3-chain gene rearrangements (20,86) and appeared to have deleted this locus contributed by the normal T-lymphocyte fusion partner (86). The observation that no new gene rearrangements were found in these STL hybridomas using a genomic J region probe suggests that the failure to detect functional 1 chain genes was not the result of rearrangements involving a V-D-J switch to a new C region isotype (86).…”