Submitted October 20, 2008
Accepted March 17, 2009
KIR acquisition probabilities are independent of self-HLA class I ligands and increase with cellular KIR expression
Sandra Andersson, Cyril Fauriat, Jenny-Ann Malmberg, Hans-Gustaf Ljunggren, and Karl-Johan Malmberg*
Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden
Bossvagen 13, Sollentuna, Sweden
* Corresponding author; email: kalle.malmberg{at}ki.se.
Inhibitory killer cell immunoglobulin-like receptors (KIRs) preserve tolerance to self and shape the functional response of human NK cells. Here, we have evaluated the influence of selection processes in the formation of inhibitory KIR repertoires in a cohort of forty-four donors homozygous for the group A KIR haplotype. Co-expression of multiple KIRs was more frequent than expected by the product rule that describes random association of independent events. In line with this observation, the probability of KIR acquisition increased with the cellular expression of KIRs. Three types of KIR repertoires were distinguished that differed in frequencies of KIR- and NKG2A-positive cells but showed no dependency on the number of self-HLA class I ligands. Furthermore, the distribution of self- and nonself-KIRs at the cell surface reflected a random combination of receptors rather than a selection process conferred by cognate HLA class I molecules. Finally, NKG2A was found to buffer overall functional responses in KIR repertoires characterized by low KIR expression frequencies. The results provide new insights into the formation of inhibitory KIR repertoires on human NK cells and support a model in which variegated KIR repertoires are generated through sequential and random acquisition of KIRs in the absence of selection.
