Identification and sequence of a fourth human T cell antigen receptor chain

Abstract

Thymus-derived lymphocytes (T cells) use clonally distributed antigen receptors to recognize peptide fragments associated with products of the major histocompatibility complex (MHC) (refs 1–4). On most murine and human T cells the T cell receptor (TCR) is composed of disulphide-linked α and β chains (TCR_α/β), each of which contains constant and variable domains, and which are associated with the invariant chains of the CD3 complex^5,6. It has been demonstrated, however, that a distinct CD3-associated TCR is expressed on a small subset of T cells or immature thymocytes which fail to express either CD4 or CD8 (refs 7–14), the molecules associated with class II or class I MHC antigen recognition. Instead of TCR_α/β, these cells express heterodimers of γ and δ chains (TRC_γ/δ). The genes encoding α, β, and γ have been isolated and characterized^15–17. A new murine T cell receptor (C_x) gene which undergoes rearrangement and expression early during T cell ontogeny has recently been identified 5′ of the murine J_αC_α gene locus¹⁸. Here we isolate and sequence the homologous transcript from PEER, a human cell line that expresses a TCR_γ/δ, and show that it encodes a protein with characteristic V, D, J, and C segments. Using probes derived from this transcript, we have shown that both PEER and MOLT-13, another TCR_γ/δ-expressing cell line, rearrange this locus and express two sizes of transcripts differing in the 3' untranslated region. Using a synthetic peptide derived from the deduced C region sequence, we have prepared antisera that precipitates the δ chain of the TCR from both PEER and MOLT-13, thus demonstrating that C_x and its human homologue code for the δ chain of the TCR.