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Prepublished online as a Blood First Edition Paper on January 2, 2003; DOI 10.1182/blood-2002-08-2568. This Article Full Text (PDF) All Versions of this Article: 2002-08-2568v1 101/9/3730    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Shilling, H. G Articles by Parham, P. Search for Related Content PubMed PubMed Citation Articles by Shilling, H. G Articles by Parham, P. Social Bookmarking                   What's this? Submitted August 21, 2002 Accepted December 17, 2002 Reconstitution of NK cell receptor repertoire following HLA-matched hematopoietic cell transplantation Heather G Shilling, Karina L McQueen*, Nathalie W Cheng, Judith A Shizuru, Robert S Negrin, and Peter Parham Department of Structural Biology, Stanford University, Stanford, CA, USA Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA Department of Medicine, Stanford University, Stanford, CA, USA * Corresponding author; email: kmcqueen{at}stanford.edu. Interactions between killer immunoglobulin-like receptors (KIR) and HLA class I ligands influence development of natural killer (NK) cell repertoire and response to infection, cancer and allogeneic tissue. As KIR and HLA class I molecules are highly polymorphic, clinical allogeneic hematopoietic cell transplantation is predicted to frequently involve KIR-mismatch, and thus to provide a unique system for study of human NK cell receptor repertoire development. Eighteen leukemia patients undergoing HLA-matched transplantation and their donors were analyzed for KIR genotype. Ten of 13 HLA-identical donor-patient pairs were KIR-mismatched and three were matched; all HLA-matched unrelated pairs were KIR-mismatched. Reconstitution of recipient NK cell repertoire following transplantation was examined using flow cytometry and monoclonal antibodies specific for KIR and CD94:NKG2A. These data form three groups. Six to nine months post-transplantation, eight patients (group 1) reconstituted an NK cell repertoire resembling that of their donor, and for KIR-mismatched transplants, distinct from the recipient pre-transplant. During the first year post-transplant five patients (group 2) exhibited a generally depressed frequency of KIR-expressing NK cells and concomitant high frequency of CD94:NKG2A expression. By three years post-transplant, the frequency of KIR-expressing NK cells had increased to donor values, in the three group 2 patients analyzed for this period. The remaining five patients experienced severe clinical complications following transplantation and displayed unique features in their NK cell receptor reconstitution. These results demonstrate that a majority of HLA-matched hematopoietic cell transplants involve KIR mismatch and reveal differences in NK cell repertoire having potential impact for immune responsiveness and transplant outcome. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. J. J. Rose, A. G. Brooks, L. A. Stewart, T. H. Nguyen, and A. P. 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