1. Is KIR- typing relevant to HCT donor selection?
Dr.Taghadosi
Assistant professor of immunology
Kermanshah university of medical center
BMT center, immunology division

2. NK cells
NK cells are lymphoid lineage with potent cytotoxic activity against tumor cells and they show alloreactivity properties in HSCT.
Less than 2% of cells in bone marrow or spleen.
5% of the lymphocytes in blood.
Two major types of NK cells
Stronger cytotoxic activities
Weaker cytotoxic activities

3. NK cell target cell recognition

4. Killer cell activating and inhibitory receptors
©2014 American Association for Cancer Research (AACR)

5. KIR proteins

7. Killer-cell Immunoglobulin Like Receptor (KIR) genes
in Leukocyte Receptor Complex (LRC) on chromosome 19

8. Two broad KIR haplotypes exist

9. KIR genes and haplotype in individuals
Numerous killer‐cell immunoglobulin‐like receptor (KIR) haplotypes with different gene content have been described.
 A haplotypes have a single arrangement of seven expressed genes that encode mostly inhibitory KIR which are diversified by allelic variation.
B haplotypes have varied gene arrangements and tend to comprise more activating genes and less allelic diversity. 
  Genotypes that are an ‘AA’, ‘AB’ or ‘BB.
Typically, a person inherits between 14 and 24 KIR genes (between 7 and 12 KIR genes per haplotype).

10. KIR nomenclature

12. 18TH INTERNATIONAL HLA & IMMUNOGENETICS WORKSHOP (IHIWS)
NGS: allelic typing for the HLA region and for KIR

13. Natural killer cell reconstitution through engraftment reconstitution
Natural killer (NK) cells are the first donor-derived lymphocyte subsets to recover after hematopoietic cell transplantation .
Preceding by several months the reconstitution of adaptive T and B lymphocytes.
They will affects various aspect of HSCT.

14. Role of NK cells in various aspects of allo-HSCT
Host NK cells persisting after conditioning can contribute to graft rejection.
Donor NK cells can promote hematopoietic engraftment.
NK cells as crucial players in preventing cancer relapse after HCT for hematologic malignancies.
Controlling post transplant infection like CMV
NK cells could either promote or prevent GvHD.

15. The concept of selecting donors by KIR genotype to optimize GVL effects after SCT for AML. 
A cohort of 261 patients with hematologic malignancies undergoing T-depleted myeloablative SCT. 
 3 donor KIR genes (2DL5A, 2DS1, and 3DS1) associated with a reduced AML relapse rate post-SCT. 

16.  KIR genotyping could be used to supplement HLA typing
to improve transplant outcome for AML by allowing the selection of donors
with favorable KIR types.

17. KIRs and their HLA class I ligands play role in the graft versus leukemia effect in AML.
It seems that HLA-C1 homozygosity improves event free survival (EFS) in patients after allo-HSCT, and KIR2DS 1-positive donors are preferable for HLA-C1patients.

18. Effect of donor KIR genes on relapse in AML patients

19. NK cell contribution to graft- versus-host disease

20. Allogeneic bone marrow transplantation and NK cell-mediated anti-viral immunity
NK cells appear to play a protective role against CMV following HSCT.