RECONSTITUTION OF NK CELL REPERTOIRE

Stanford University, Stanford CA

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Abstract

Natural killer (NK) cells are lymphocytes that act early in the immune response. They can kill infected and allogeneic cells, secrete cytokines and contribute to inflammation. The actions of human NK cells are regulated by two families of cell-surface molecules, CD94:NKG2 and KIR, which include receptors that bind polymorphic determinants of HLA class I molecules. By differential expression of combinations of these genes, NK cells become highly diversified within each individual. Due to differences in gene number, gene content, and allelic polymorphism of KIR gene haplotypes NK cell receptor repertoires vary within the human population. In addition to possible contributions to alloreactions following transplantation, these properties provide new tools for assessing factors that influence NK cell receptor development. Under test is the hypothesis that NK cell receptor repertoires are genetically determined in patients receiving HLA-matched allogeneic bone marrow grafts. The NK cell repertoires of the donors and of the recipient, before and after transplant, will be characterized. The hypothesis genes encoding the HLA class I ligands play a lesser role. Similar study of autologous transplants will provide a control for effects due to disease and therapy. Another control will come from assessment of NK-cell repertoire differences in healthy siblings having defined and variable degrees of HLA, KIR, and CD94:NKG2 identity. The results will provide valuable information on the nature, development, and reconstitution of the human NK-cell repertoire after bone marrow transplantation.