Evaluation of the structure function relationships of MHC class I antigens by molecular genetic techniques.

By combining the knowledge gained from several types of experiments we are beginning to understand the functional role of many structural features of the MHC class I antigens. Studies done by exon shuffling have defined the domains involved in recognition by T-cells and antibodies. As a result, we now know that the interaction between domains, as well as the structure of individual domains, is important for immune recognition. By in vitro mutagenesis we have shown that N-linked carbohydrate moieties appear to function primarily in facilitation of intracellular processing, having seen little effect on immunologic function by their removal. Two other highly conserved structures, the disulfide bridges of the C-1 and C-2 domains, appear by this methodology to function in both intracellular processing and immune recognition. Finally, we are hopeful that extension of the method of in vitro mutagenesis to the evaluation of individual polymorphic amino acids in the MHC class I antigens will yield significant information regarding the relationship of their structure to their function.