The T lymphocyte antigen receptor. A critical review of recent experimental literature

The search for the true nature of the T-cell receptor for antigen has been impeded by several factors including: (1) the relatively low density of antigen binding receptors on T cells: (2) the lack of large quantities of homogeneous T cells for analysis; (3) the inability to study the T receptor protein independent of the T-cell surface; (4) the greater degree of complexity of the receptor compared to conventional immunoglobulin, and (5) possibly the relatively low binding affinity of the receptor for free antigen. Despite these impediments extensive immunobiological evidence has accumulated that the T receptor possesses idiotypic determinants analogous to those of conventional immunoglobulins on the B-cell surface. When both T and B cells recognize the same antigenic determinant they share a common idiotypic determinant. Nonetheless, recent evidence from methods examining gene expression in T cells speaks against VH gene expression. Thus, it appears that two entirely different gene pools, and possibly different mechanisms, have evolved in B and T cells to generate the equally vast diversity of immunoglobulins and T-antigen-receptor molecules. MHC products play a central role in T-cell receptor function by governing intercellular interactions through MHC restriction. MHC restriction is a property acquired by T cells during intrathymic maturation. The function (if any) of MHC products on the T-cell surface remains unknown, although much evidence suggests that the T receptor must be able to recognize MHC products in association with antigen on antigen-presenting cells. The altered-self theory seems to best explain the constraints governing the T receptor's recognition of antigen plus MHC product on the antigen-presenting cell. The differentiation antigens on the T-cell surface defined by monoclonal antibodies have proven extremely useful as markers of functionally distinct T-cell subsets. More recently a function role for three of these antigens, T3, T4, and T8 has been discovered. The T3 antigen now appears to be intricately associated with the antigen-specific (or clonotypic) T-receptor molecule so as to promote antigen recognition. In addition, low concentrations of anti-T3 are mitogenic for T cells suggesting another possible function for the T3 molecule. The T8 and T4 molecules seem to recognize class I and class II MHC determinants, respectively, in a manner which governs cytotoxicity toward cells expressing these MHC determinants. The advent of T-cell clones and T-cell hybridomas has overcome many of the impediments toward the search for the T receptor.(ABSTRACT TRUNCATED AT 400 WORDS)