IDENTIFYING T CELL LIGANDS IN SARCOIDOSIS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Sarcoidosis is a systemic disorder of unknown etiology which affects the lung in greater than 90% of cases. This disease is characterized by an accumulation of activated CD4+ T cells in the lung and other sites of disease activity, and evidence strongly suggests that these T cells are intimately involved in the development of sarcoidosis. These CD4+ T cells express a unique receptor on their surface, known as the T cell receptor (TCR), that recognizes a specific peptide antigen. There are approximately 107 different TCRs expressed by these T cells, thus generating a diverse T cell repertoire and allowing the body to recognize and generate an immune response to a diverse number of antigens. In sarcoidosis, lung CD4+ T cells with increased expression of particular TCRs, for example Va2.3, have been shown. Individuals with expanded bronchoalveolar lavage (BAL) Va2.3 subsets usually express the HLA-DR allele, DRB1*0301. These expansions are only present in the lung and disappear with disease remission, reinforcing their importance in the disease process. One difficulty in working with BAL T cell clones is that these cells can be expanded in culture for only a short period of time before dying. In this proposal, we will enroll active sarcoidosis patients expressing both DRB1*0301 and TCR Va2.3 BAL expansions and use a novel approach to define the T cell ligands in sarcoidosis. This novel approach will generate "mimotopes" which can be screened against known peptide/protein sequences and will provide new insight into the etiologic sarcoidosis antigen.