The processes of immune recognition and response by T cells central to immunogiology. The repertoire of cellular interaction involved is dependent on complex structures present on the T cell surface. To date, the greatest advances in identifying these molecules have come from serological analyses. Mouse monoclonal antibodies have revealed a large array of T cell specific determinants on human mouse T cells. Among the molecules identified are the clonal distributed, antigen-specific """"""""T cell receptors"""""""" and a number of polymorphic, """"""""accessory"""""""" structures. Not all of the invariant class molecules observed in the human have been identified in the mouse. An example, a murine equivalent of T3, a human pan-T cell complement intimately associated with the T cell receptor, has not yet been found. This may be due to inherent limitations of an immunological approach and it may reflect distinct ways of creating functional T cell structures. A genetic analysis of T cell activity offers a means of identifying and understanding the structures involved and the roles that they play. In this proposal, two genetic approaches are described which focus on the mouse T cell. Classical somatic cell mutant isolation will begin with selections employing available T cell reactive antibodies. Mutant characterization will be made by functional, immunological, biochemical and fenetic criteria. Mutations which identify loci other than that encoding the protein to which the selecting antibody is directed will identify genes and gene products which are functionally involved in cell activity. A second genetic approach will use transfection scheme to create phenotypic mutations in genes of interest. Expression methods will be used to abolish gene activity and examine the resulting phenotypes with respect to structure and function. The data obtained from these genetic studies will provide independent evaluation of the requirements for the biological process of recognition and response by T cells.
| Ucker, D S; Ashwell, J D; Nickas, G (1989) Activation-driven T cell death. I. Requirements for de novo transcription and translation and association with genome fragmentation. J Immunol 143:3461-9 |
