KIR Ligand Calculator

Recent transplant strategies based on KIR-ligand mismatch to predict NK cell alloreactivity have resulted in less relapse, less GvHD and better overall survival in patients with Acute Myeloid Leukaemia (AML) (1). KIR-ligands are HLA molecules that can be grouped into three major categories based on the amino acid sequence determining the KIR-binding epitope in HLA-C and HLA-B molecules. All expressed HLA-C alleles are of the C1 or C2 group (2) and most HLA-B alleles can be classified as either Bw4 or Bw6 (3). The grid below shows how the tool defines these groups. Killer-immunoglobin receptors KIR2DL1, KIR2DL2 and KIR3DL1 bind KIR-ligand C2, C1 and Bw4 respectively, resulting in inhibition of NK cell mediated lysis.

Locus Motif 77 80
HLA-B Bw4 N (Asparagine) I (Isoleucine )
HLA-B Bw4 N (Asparagine) T (Threonine)
HLA-B Bw4 D (Aspartic acid) T (Threonine)
HLA-B Bw4 S (Serine) T (Threonine)
HLA-B Bw6 G (Glycine) N (Asparagine)
HLA-B Bw6 S (Serine) N (Asparagine)
HLA-C C1   N (Asparagine)
HLA-C C2   K (Lysine)

The IPD-KIR Ligand Calculator has been written in collaboration with Jeff Miller, University of Minnesota, USA.

Search for Mismatches Between KIR Ligands

Disclaimer - Clinical NK cell alloreactivity may be affected by many variables. This research tool is being offered as a tool only and makes no claims in support for or against the use of the KIR-Ligand mismatch strategy in clinical transplantation or others settings testing the use of NK cell alloreactivity.

Search for Mismatches Between KIR Ligands
Patient HLA-B* HLA-B* HLA-C* HLA-C*
Donor HLA-B* HLA-B* HLA-C* HLA-C*
 

  • Enter the four digit typings in the box provided. For example for an individual typed as B*07:02, B*08:01, C*07:01, C*07:02, you would enter 07:02 in the first box, 08:01 in the second box and so on. The gene is already entered, so only the numerical part of the name needs adding.
  • If an individual is homozygous for a locus enter the typing in all boxes. Do not leave a box blank.
  • Null alleles are not expressed so please do not enter null alleles into the box provided. Please note that two digit typings may be entered. In these cases the output will list the main ligand for the two digit typing and any exceptions. Care should therefore be taken when reviewing any results as although the exceptions may be due to rare alleles; they should not be discarded from any analysis.

Output

  • The output lists the ligands associated with the typing entered. In the case of two digit typings the most common ligand for the allele type is displayed.
  • A link to the full list of alleles matching the type given and their associated ligands is provided.
  • For two digit typings any exceptions are listed, along with their motif. For example B*15 alleles are predominately Bw6 however there are a number of alleles, B*15:13, which have the Bw4 motif.
  • The output classifies alleles in the exceptions list as "Rare" if they have a gene frequency of less than 0.001 and have been seen in less than 3 unrelated individuals (4).

References

All references are linked to the Medline abstract where possible.

  1. Ruggeri L, Capanni M, Casucci M, Volpi I, Tosti A, Perruccio K, Urbani E, Negrin RS, Martelli MF, Velardi A.
    Role of natural killer cell alloreactivity in HLA-mismatched hematopoietic stem cell transplantation.
    Blood (1999) 91:333-9 (Abstract)
  2. Khakoo SI, Thio CL, Martin MP, Brooks CR, Gao X, Astemborski J, Cheng J, Goedert JJ, Vlahov D, Hilgartner M, Cox S, Little AM, Alexander GJ, Cramp ME, O'Brien SJ, Rosenberg WM, Thomas DL, Carrington M. (2004)
    HLA and NK cell inhibitory receptor genes in resolving hepatitis C virus infection.
    Science 305:872-4 (Abstract)
  3. Gumperz JE, Barber LD, Valiante NM, Percival L, Phillips JH, Lanier LL, Parham P.
    Conserved and variable residues within the Bw4 motif of HLA-B make separable contributions to recognition by the NKB1 killer cell-inhibitory receptor.
    J Immunol. (1997) 158:5237-41 (Abstract)
  4. Cano P, Klitz W, Mack SJ, Maiers M, Marsh SGE, Noreen H, Reed EF, Senitzer D, Setterholm M, Smith A, Fernandez-Vina F.
    Common and well-documented HLA alleles. Report of the Ad-Hoc committe of the american society for histocompatibilty and immunogenetics.
    Hum Immunol. (2007) 63:392-417 (Abstract)

IPD-KIR