Arsonate-specific murine T cell clones. I. Genetic control and antigen specificity

Abstract

Thymus-derived lymphocytes exert a number of regulatory and effector activities in the immune system. Evidence has accumulated in recent years that these activities are largely executed by distinct subsets of T cells that can be distinguished by particular cell surface antigens (1, 2). This has led to the concept of a complex network of T cell types, each endowed with its own specific function. Rigorous proof of this concept has been difficult to achieve with heterogeneous cell populations. Recently, it has been possible to establish and maintain for prolonged periods in culture antigen-specific T cell lines (3, 4), paving the way to a more definitive approach to this question. Homogeneous populations of antigen-specific T cells should also prove extremely useful for studies of the chemical nature of the antigen in its activating form, as well as the nature of the T cell antigen receptor itself. In addition, comparison of these parameters between different functional subsets of T cells specific for the same antigenic determinant should be possible.We report here the establishment, genetic control, and preliminary characterization of the antigen specificity of normal T cell lines specifically responsive to a structurally defined epitope, L-tyrosine-p-azobenzenearsonate (ABA-Tyr)) It had been established previously (5, 6) that this simple synthetic compound is immunogenic in guinea pigs and mice. Accordingly, A/J mice were immunized with ABA-Tyr, and lymph node cells from the immune animals were used to establish antigen-reactive T cell lines. Strain A/J mice were chosen for this purpose because their anti-ABA antibody response is dominated by a major cross-reactive idiotype (7), providing the possibility of useful markers for the purification and characterization of T cell antigen-specific molecules as well as studies of the regulation of idiotype expression in antibody responses. The functional activity of these ABA-Tyr-specific T cell lines will be the subject of another communication.

Activation specificity of arsonate-reactive T cell clones. Structural requirements for hapten recognition and comparison with monoclonal antibodies.

“…Early work using heterogeneous hapten-reactive T cells showed that T cells, like antibodies, could discriminate between related haptens (1,2,(4)(5)(6). Studies with clones of helper and cytolytic T cells have confirmed this conclusion (7)(8)(9). The premise of our work was that by using hapten-reactive T cell clones and hapten analogues, the structural features of a hapten that were important for activation might be identified.…”

“…The most selective T cells show at least the ability of antibodies to make fine discriminations between arsonate and its analogues. Certain immunization regimens may elicit primarily the selective antibodies (34,36) or the selective T cells (4,9), while others elicit both classes of response (this study).…”

Molecular analysis of original antigenic sin. I. Clonal selection, somatic mutation, and isotype switching during a memory B cell response.

“…Perhaps this lower affinity results in lower levels of the type of T cell help (e .g ., Th2) required for isotype switching to IgGI due to less efficient B cell antigen capture, resulting in lower levels of antigen presentation to Th cells. Alternatively, a significant fraction of the memory Th population may have been primed to Ars (42,43), or an epitope that consists of an Ars-modified peptide subfragment of KLH. If this were true, the Sulf-KLH boost may not cross-stimulate the Ars-KLH-induced memory Th population as efficiently as it does the Ars-KLH-induced memory B cell population, perhaps leading to lower levels of isotype switching.…”

The Complexity of Structures Involved in T-Cell Activation

“…Different functional types of T cells have been induced that are specifi c for ABA including helpers (5, 6, 62), suppressors (109,161), killers (154), and mediators of delayed hypersensitivity reactions (11, 169). Very recently, long-term cultures of T cells specifically reactive to ABA-T were established from the lymph node cells of A/] mice, which had been immunized with ABA-T, and the cells were cloned by limiting dilution (70). The MHC restriction of the antigen-induced proliferation response of the clones was assayed with accessory cells from appropriate recombinant strains of mice and monoclonal anti-Ia antibodies as blocking reagents.…”