Soluble T Lymphocyte Antigen-Specific Molecules

Abstract

The immune response is characterized by the recognition of self versus nonself, specificity, in-ducibility, and memory. These hallmarks are manifested by the activity of lymphocytes, their differentiated progeny, and some of their soluble products. Specificity of the immune response is ultimately due to cell membrane receptors of T and B lymphocyte clones which bind specifically to antigen. This interaction results in a complex series of events leading to expansion and differentiation of the responding clones, and immunologic memory of the previous exposure to the antigenic stimulus. B lymphocytes extend their specific recognition of antigen by the production of soluble, antigen-specific immunoglobulins with combining sites identical (or very similar) to the heavy and light chain V regions of the B cell membrane immunoglobulin receptor (1) for antigen. In contrast to B lymphocytes, most antigen-specific T lymphocyte activity is mediated by cell membrane-associated receptors which recognize fragments of antigen processed by antigen-presenting cells and associated with class I or II major histocompatibility gene complex (MHC) products (2). The T cell receptor (TCR) for antigen is a heterodimeric molecule consisting of α- and β- or γ- and δ-chains linked by disulfide bonds (2–4), and the organization and sequence of T cell receptor genes demonstrate a significant similarity to immunoglobulin V region genes (3, 4). In addition, murine and human TCR β-chains and immunoglobulin light chains bear cross-reactive epitopes detected by antibodies to synthetic peptides corresponding to the TCR Vβ region (5). However, only low affinity binding of nominal antigen by T cell receptor α-chains has been demonstrated (6). This may be due to conformational changes in the molecule in an aqueous environment and the nature and amount of antigen used. In addition, the affinity of T cell receptors for nominal (non-MHC associated) or MHC-associated antigen may be too low to demonstrate specific binding by conventional methods.