BASIS OF DETERMINANT RECOGNITION BY THE IMMUNE SYSTEM

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This program project brought together a group of investigators whose primary interests concerned determinant recognition by the immune system but whose individual expertise ranged from the analysis of protein structure to the parameters of B cell and T cell stimulation. A major new initiative in this program is represented by project IV in which Dr. Paterson is proposing an independent project to continue her studies (from project III) on the structural requisites for the recognition by B cells and T cells of defined peptides of cytochrome c. The addition of NMR studies provided by Dr. Wright to this program will aid not only these studies but will be central to the proposal of Dr. Lerner (project II) who plans to further refine findings that indicate that anti-peptide antibodies preferentially bind to proteins, if the peptide is derived from a region of the protein with high molecular mobility. These studies plus those of Dr. Wilson (project I) wherein the three-dimensional structure of the PR8 hemagglutinin (HA) and related peptides will be analyzed with respect to their interactions with monoclonal antibodies, will provide structural underpinnings for the projects in this program that focus on the contributions of immunocyte selection to determinant recognition. For example, Dr. Sherman in project VI will follow up on her early predictions that CTL specificity is predicated on the recognition of novel conforms of self MHC antigens. In addition to her studies of H-2b mutants she will also analyse antigens expressed on transfected cells and in transgenic mice. In a similar fashion, Dr. Chiller in project V will study helper T cell recognition of exon-shuffled class I MHC genes and of foreign antigens. The mechanism by which non-recognition of self determinants is induced and maintained will continue to be studied by Dr. Klinman in project III and Dr. Bevan in project VII. Project VII will focus on the role of "veto" cells in surveillance and maintenance of self recognition whereas project III will continue to assess the role of self MHC in shaping the B cell repertoire and, in collaboration with Drs. Sherman and Chiller, will attempt to construct transgenic mice expressing the influenza HA as a "pseudo-self antigen".