PrincipInavlestigator/PDroirgercat(omLrasfitr,stm, iddle): Shastri, NiIabh DESCRIPTION: State the application's broad, long-term objectives and specific aims, making reference to the health relatedness of the project. Describe concisely the research design and methods for achieving these goals. Avoid summaries of past accomplishments and the use of the first person. This abstract is meant to serve as a succinct and accurate description of the proposed work when separated from the application. If the application is funded, this description, as is, will become public information. Therefore, do not include proprietary/confidential information. DO NOT EXCEED ]'HE SPACE PROVIDED. The long term goal of this research is to understand and thus manipulate the antigen-specific interactions between the ocl3T cell antigen receptor (TCR) and its peptide/MHC ligand. We have chosen to study the TCR/ligand interactions in the mouse minor histocompatibility (H) antigen models. Using novel methods developed in our laboratory we have isolated five different polymorphic H antigen genes (H3a, H13, H28, H47 and H60) that elicit potent CD8 T cell responses when appropriate host mouse strains are immunized with donor cells differing at one or more of these H loci. We have also developed new methods for identifying CD4 T cell stimulating antigen genes which up until now have remained virtually unknown because of extraordinary technical difficulties. Here we propose to identify currently unknown CD4 T cell stimulating H antigen genes to test the hypothesis that these may be different from those that elicit CD8 T cell responses and could represent an unique sub-set of polymorphic proteins. We will use these new H antigens together with the known H antigens to further test the hypothesis that CD4 and CD8 T cell responses can be elicited to the same H antigens regardless of the MHC haplotype. Finally, we have determined that a hierarchy exists among the CD8 T cells in response to multiple H epitopes. We will determine whether this epitope hierarchy is due to differences in direct or indirect presentation of donor H peptide/MHC or the host T cell repertoire. We expect the findings to reveal new insights into the nature of endogenous peptides presented by MHC class II and MHC class I molecules in normal cells as well as fundamental issues in transplantation immunology. PERFORMANCE SITE ========================================Section End===========================================
| Blanchard, Nicolas; Shastri, Nilabh (2008) Coping with loss of perfection in the MHC class I peptide repertoire. Curr Opin Immunol 20:82-8 |
