GENERATION AND CHARACTERIZATION OF 2 HUMAN ALPHA BETA T-CELL CLONES -RECOGNIZING AUTOLOGOUS BREAST-TUMOR CELLS THROUGH AN HLA-INDEPENDENT AND TCR/CD3-INDEPENDENT PATHWAY/

Cell-mediated immune response to breast tumor has only been marginally investigated. To gain insight into this issue we have developed two c lones of distinct phenotype, CD3(+) alpha/beta, CD4(+), CD8(-), CD16(- ), and CD3(+) alpha/beta, CD4(-), CD8(+), CD16(-), respectively, from peripheral blood lymphocytes (PBL) of a breast cancer patient. These e ffecters, selected on the basis of their cytolytic activity against au tologous tumor cells and lack of lysis on NK-sensitive cell lines, pre ferentially recognize autologous tumor cells. The two clones' cytotoxi c activity, while inhibited by anti-LFA-1 mAb, could not be abolished by mAbs to CD3, to class I and class II MHC molecules, and by mAbs to molecules involved in T cell function (i.e., CD4, CD8, CD2). The molec ular structure of the alpha and beta T cell receptor chains of the two effector cells, confirmed their clonality and showed that, despite an overlapping killing pattern, they possess distinct TCR alpha and beta chains. These findings demonstrate that breast tumor-specific CTL clo nes can be generated through current technology and that a alpha/beta effector cell population operating through a HLA-unrestricted and TCR/ CD3-independent pathway may be involved in the identification and kill ing of this tumor.