Interactions between lymphocytes through idiotype recognition are believed to play a central role in the regulation of cellular as well as humoral immune responses. Consequently, perturbation of the balance in an idiotype network may often result in an autoimmune disease. To better understand the regulatory mechanisms and the idiotype interactions of lymphocytes involved in antibody production, T cell antigen receptors reactive with the hapten, phosphorylcholine (PG), in conjunction with either specific or non-specific carriers will be analyzed. Structural and sero-logical studies of T cell receptors reactive to PG offer unique advantages because (1) an extremely limited repertoire of antibodies, as well as T cells specific for the epitope appear to be expressed, and (2) it has been suggested by functional studies that the predominant idiotype of anti-PG antibodies is shared by the PG- reactive T cell antigen receptors, providing an excellent model system for studying idiotype- mediated immune regulation. We propose here to analyze the T cell antigen receptors reactive to PG- antigens and to investigate the idiotypic relationship between the epitope-reactive T cells and antibodies. We will approach these objectives, first, by selecting a number of T cell hybridomas reactive with PG in conjunction with either specific or non-specific carriers. These hybridomas will then be categorized based on their fine epitope specificity, including the extent of cross-reaction with hapten analogs and any additional residues required for their activation other than PG. The influence of haptenization on the host response to PG and/or carrier will also be studied using mouse strains with different responsiveness to the antigens. The possible serological cross-reactivity among the T cell clonotypes and/or with idiotypes of anit-PG antibodies will be examined by using monoclonal antibodies specific for the T cell hybridoma clones and for the major idiotype of anti-PG antibodies. Finally, cDNA representing the mRNA coding for the PG-reactive T cell receptors will be molecularly cloned and sequenced to correlate the structure of T cell receptors with their specific antigen recognition. These studies will provide valuable information on the mechanisms of T cell recognition of haptens and hapten-modified antigens as well as their possible involvement in the idiotype network of the anti-PG response.
Showing the most recent 10 out of 14 publications
