Epitopes of I-Ak Involved in Antigen Presentation to T-Cell Hybridomas
The discovery of MHC-restricted recognition of foreign antigens by cytotoxic and helper T lymphocytes marked a fundamental breakthrough in our understanding of antigen recognition by T cells and simultaneously provided the first convincing explanation for the physiologic function of MHC Class I and Class II molecules. However, fourteen years after the first description of MHC-restricted antigen recognition, the molecular details of the implied ternary complex involved in that recognition, i.e. processed antigen, MHC product, and T cell receptor, have yet to be described in depth. Primarily due to technical complexities of the system, it is only in the last two to three years that the problem has been examined at the biochemical level. Three basic approaches have been taken thus far. The first has been an examination of how the structure of the antigen itself influences the antigen presentation process, specifically which residues contact the T cell receptor or the Ia molecule (Ashwell et al. 1986, Guillet et al. 1986, Sette et al. 1987). The second approach has been to carry out molecular modelling of the T cell receptor in order to predict its potential binding sites (Novotny et al. 1986). The third approach has been to examine what effect Ia structure has on antigen presentation (Allen et al. 1985, Beck et al. 1986, Cohn et al. 1986, and Lechler et al. 1986) and specifically on the interaction of Ia with processed antigen (Buus et al. 1987) and with the T cell receptor. Our laboratories have recently adopted the third approach to dissecting the ternary complex of Ia, processed antigen and T cell receptor.
KeywordsCell Receptor Antigen Presentation Hypervariable Region Direct Binding Assay Antigen Presenta
Unable to display preview. Download preview PDF.
- Beck, B. N., Pease, L. R., Bell, M. P., Buerstedde, J. M., Nilson, A. E., Schlander, G. G., and McKean, D. J.: DNA sequence analysis of I-Aß mutants reveals serologically immunodominant region. J. Exp. Med. In press, 1987.Google Scholar
- Lechler, R. I., Ronchese, F., Braunstein, N. S., and Germain, R. N.: I-A-restricted T cell antigen recognition. Analysis of the roles of Aa and Aß using DNA-mediated gene transfer. J. Exp. Med. 163: 678696, 1986.Google Scholar
- Sette, A., Buus, S., Colon, S., Smith, J. A., Miles, C., and Grey, H. M.: Structural characteristics of an antigen that are required for its interaction with Ia and recognition by T cells. Nature In press, 1987.Google Scholar