The role of accessory and adhesion molecules in MHC-unrestricted T cell recognition of the tumor specific antigen MUC-1

MUC-1 is a tumor specific antigen that has been shown to be recognized by T cells independently of the MHC presumably due to the presence of a tandemly repeating 20 amino acid sequence that serves as the T cell epitope. The presence of an array of these MUC-1 epitopes may engage the T cell receptors simultaneously and with enough affinity to send a stimulatory signal to the T cell. We have generated cytotoxic T cell lines (CTL) by in vitro stimulations with either alternating allogeneic breast tumor cell lines or MUC-1 transfected C1R cells. These CTL were used to study the role of adhesion or accessory molecules in the MHCunrestricted recognition of MUC-1. We have found that the CTL were capable of killing MUC-1 22 repeat transfected C1R or T2 cells but not MUC-1 2 repeat transfected C1R or T2, or untransfected controls. Recognition of MUC-1 2 repeat transfected C1R was restored upon transfection of a single HLA allele. We hypothesize that when a small number of MUC-1 repeats is present, MHC Class I may be necessary to engage CDS and complete the stimulatory signal to the T cell. Using antibody blocking, we are also studying the roles of adhesion molecules such as CD54 and CD58 in MHC-unrestricted recognition of MUC-1 on tumor cells, and how it compares to their role in recognition of the same tumor cells by an alloreactive T cell line.