In a recent study, published in the September 11 issue of Blood (impact factor 10.6), Niklas Björkström and Karl-Johan Malmberg at Karolinska Institutet and Department of Immunology, Institute for Cancer Research, OUS, respectively, examined killer cell immunoglobulin-like receptors (KIRs) expression patterns on CD8 T cells.
Epistatic interactions between KIRs and their cognate HLA class I ligands have important implications for reproductive success, anti-viral immunity, susceptibility to autoimmune conditions and cancer, as well as for graft-versus-leukemia reactions in settings of allogeneic stem cell transplantation.
Although originally discovered on natural killer (NK) cells, a large fraction (on average 30%) of the terminally differentiated effector T cell population was found to express KIRs. Despite similarities in the stochastic regulation of KIRs by the bi-directional proximal promoter, the specificity of inhibitory KIRs on CD8 T cells was often distinct from that of NK cells in the same individual. Finally, the study demonstrates that KIR-expression down-modulate the functional responses of CD8 T cells in an HLA-independent manner.
The findings challenge the notion that inhibitory self-KIRs are involved in fine-tuning of functional responses and being essential for survival of CD8 T cells during clonal expansion. Further studies of complete KIR repertoires of both NK cell and CD8 T cells should clarify factors underlying the relationship of KIRs and HLA class I genes to disease.
CD8 T cells express randomly selected KIRs with distinct specificities compared to NK cells
Niklas K. Björkström, Vivien Béziat, Frank Cichocki, Lisa L. Liu, Jeffrey Levine, Stella Larsson, Richard A. Koup, Stephen K. Anderson, Hans-Gustaf Ljunggren and Karl-Johan Malmberg
Blood; published ahead of print September 11, 2012
Abstract - Full text (PDF) - Supplemental Figures and Tables
Blood - weekly medical journal published by the American Society of Hematology.
Karl-Johan Malmberg's group - Natural Killer Cell Biology and Cell Therapy
Department of Immunology
Institute for Cancer Research