Immunoglobulin-like nature of the α-chain of a human T-cell antigen/MHC receptor

Abstract

Although the receptor with which T cells bind specific antigen can, like immunoglobulin, distinguish between antigens which differ only slightly in structure, it is unique in recognizing antigen only in conjunction with one of the self proteins of the major histocompatibility complex (MHC restriction)^1–4. The receptor was identified and characterized in mouse and man by using monoclonal antibodies to receptor idiotypes^5–7, and consists of two disulphide-linked polypeptides, an acidic α-chain and a neutral to slightly basic β-chain^5,8,9. Peptide maps have shown that, like immunoglobulin, both chains vary for receptors of different specificities^10–12. T-cell-derived cDNA clones have recently been identified in mouse and man encoding immunoglobulin-like molecules^13–15. These were identified as derived from β-chain genes through a partial N-terminal protein sequence of the β-chain isolated from a human T-cell tumour¹⁶. We have now purified the α- and β-chains of the receptor of the human T-cell leukaemia line HPB-MLT, and have determined the amino acid sequence of several tryptic peptides derived from each chain. Our results further confirm that the previously reported cDNA clones encode β-chains. The sequence of the α-chain peptides identify this as another immunoglobulin-like polypeptide chain. Particularly striking was an α-chain peptide with high homology to the conserved portion of the immunoglobulin J segment and T-cell receptor β-chains. Surprisingly, the α-chain peptides show little similarity to the sequence predicted by two overlapping putative murine α-chain cDNA clones¹⁷.