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Gamma-delta T cell recognition of autologous tumor

Posted on:1997-03-22Degree:Ph.DType:Dissertation
University:Stanford UniversityCandidate:Kim, Hubert TackyoungFull Text:PDF
GTID:1464390014980337Subject:Health Sciences
Abstract/Summary:
T cells express two mutually exclusive classes of antigen receptor: the well characterized {dollar}gammadelta{dollar} T cell receptor (TCR), and the less well understood {dollar}gammadelta{dollar} heterodimer. While much has been learned about {dollar}gammadelta{dollar}+ T cells over the past several years, a general understanding of their role in the immune response remains elusive. {dollar}gammadelta{dollar}+ T cells have been postulated to act as a surveillance mechanism which eliminates transformed or otherwise damaged cells; however, very little is known about tumor recognition by {dollar}gammadelta{dollar}+ T cells. Of particular importance is a better understanding of the antigens that are recognized and the molecules that present them.; In studies of autologous tumor cell recognition, it was noted that human peripheral blood lymphocytes stimulated by autologous Burkitt's lymphomas gave rise to tumor-specific cytotoxic T lymphocytes (CTL) which expressed the {dollar}gammadelta{dollar} TCR. Here we report that these {dollar}gammadelta{dollar}+ CTL lyse heterologous cells transfected with the tumor immunoglobulin light chain gene. Furthermore, the immunoglobulin light chain is recognized as processed peptide in an idiotype-specific manner. T cell recognition does not involve classical major histocompatibility complex molecules, but could be blocked by antibodies directed against the heat shock protein grp75. In addition, co-transfection experiments using the {dollar}betasb2{dollar}-microglobulin ({dollar}betasb2{dollar}-m) deficient cell line DAUDI indicate that {dollar}betasb2{dollar}-m expression is required for recognition. These findings show that {dollar}gammadelta{dollar}+ T cells can recognize highly polymorphic antigens such as tumor idiotype, and implicate heat shock protein and a {dollar}betasb2{dollar}-m associated molecule in the presentation of antigen to {dollar}gammadelta{dollar}+ T cells.
Keywords/Search Tags:Cell, {dollar}gammadelta{dollar}, Tumor, Autologous
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