The Antigen Receptor of Thymus-Derived Lymphocytes: Progress in the Characterization of an Elusive Molecule

Abstract

Abstract

Thymus-derived lymphocytes (T cells) show remarkable specificity in their capacity to recognize non-self antigens and this recognition must serve as the initial step in the differentiation of immunologically competent T cells into antigen-specific effector cells including helpers, suppressors, and cytotoxic lymphocytes. The problem of determining the molecular nature of the receptor for antigen on these cells is a challenging area of investigation, and considerable insight into the serological and molecular properties of this receptor has recently been obtained using antibodies directed against immunoglobulin combining site regions as probes for the detection and isolation of the T-cell molecules. This review stresses results obtained within the past 3 years and (1) addresses the expression of immunoglobulin variable region determinants on T-cell receptors and factors, (2) presents a serological and molecular comparison of the structure of T-cell antigen-specific regulatory factors with those of receptors, and (3) presents a theoretical discussion of the genetics of antigen-specific T-cell factors and receptors. A pattern is emerging which indicates that T-cell receptors and some factors have a combining site which is related to immunoglobulin heavy chain variable regions. These molecules apparently do not bear determinants specified by the major histocompatibility complex (MHC), but express Ig-related variable regions and constant regions unique to T-cell products. The genes encoding these antigen-specific molecules (receptors, helper and suppressor factors) apparently are associated with the immunoglobulin heavy chain gene cluster. The intact V_H-related T-cell molecules have a subunit mass of approximately 68,000 daltons and can form disulfide-bonded dimers. Studies using proteolytic enzymes, coupled with antigenic and functional analyses, indicate that the molecule is composed of domains resembling those of immunoglobulin heavy chains, although the T-cell molecule does not bear classical heavy chain isotypic determinants. The formation of active suppressor or helper factors often requires association of V_H-related molecules with MHC-encoded proteins.