Antigen presentation by human melanoma cells expressing histocompatibility class II antigens and its relationship to autologous T cell immunity
Abstract
Biologically early primary melanoma has been shown to evoke an antigen driven T cell response which becomes attenuated with the evolution of the metastatic phenotype. Melanoma cells of early disease act as competent antigen presenting cells, presenting model (tetanus toxoid) antigens in association with HLA-class II molecules to CD4$\sp+$ T helper cells. This function is lost with tumor progression. Also the HLA-class II dependent autologous T cell response to melanoma was found to be similar to the above model in that it was sensitive to agents that inhibit 'classical' antigen presentation. Therefore tumor antigens seen in the context of HLA-class II antigens by peripheral blood T cells seem to be actively presented by stimulating tumor cells. HLA-DR proteins isolated from metastatic melanoma cells, unlike those from early primary disease, do not present antigen in an artificial membrane system. To further implicate dysfunction of these proteins in tumor progression we have infected tumor cell lines with a retroviral vector containing highly characterized, full-length HLA-DR$\beta$1 cDNAs. Finally, HLA-DR positive metastatic melanoma cells, previously unable to present antigen, that were transduced with HLA-DR-$\beta$1 genes successfully presented antigen to antigen-specific, HLA-DR-matched T cell clones. These findings suggest that in the course of tumor progression a pathway to evade the host immune response is through evolving abnormalities in HLA-class II proteins.
Subject Area
Cellular biology|Immunology
Recommended Citation
Alexander, Michael Allen, "Antigen presentation by human melanoma cells expressing histocompatibility class II antigens and its relationship to autologous T cell immunity" (1992). Dissertations available from ProQuest. AAI9235107.
https://repository.upenn.edu/dissertations/AAI9235107