|
|
Blood, 15 September 2008, Vol. 112, No. 6, pp. 2369-2380.
Prepublished online as a Blood First Edition Paper on June 26, 2008; DOI 10.1182/blood-2008-03-143727.
 Previous Article | Next Article 
Submitted March 7, 2008
Accepted June 10, 2008
MHC class I-specific inhibitory receptors and their ligands structure diverse human NK cell repertoires towards a balance of missing-self response
Makoto Yawata*, Nobuyo Yawata, Monia Draghi, Fotini Partheniou, Ann-Margaret Little, and Peter Parham
Structural Biology, Stanford University School of Medicine, Stanford, CA, United States
Histocompatibility Laboratories, The Anthony Nolan Trust, London, United Kingdom
Haematology, The Royal Free Hospital, London, United Kingdom
* Corresponding author; email: myawata{at}stanford.edu.
Variegated expression of six inhibitory HLA class I-specific receptors on primary NK cells was studied using high-dimension flow cytometry in 58 human individuals to understand the structure and function of NK cell repertoires. Sixty-four subsets expressing all possible receptor combinations were present in each repertoire and the frequency of receptor-null cells varied amongst the donors. Enhancement in missing-self response between NK subsets varied substantially where subset responses were defined by donor KIR/HLA allotypes, reflecting the differences in interaction between inhibitory receptors and their ligands. This contrasted to the enhancement conferred by NKG2A which was constant and of intermediate strength. We infer a mechanism that modulates frequencies of the NK subsets displaying diverse levels of missing-self response, a system which reduces the presence of KIR-expressing subsets that display either too strong or too weak a response and effectively replaces them with NKG2A-expressing cells in the repertoire. Through this high-resolution analysis of inhibitory receptor expression, five types of NK cell repertoire were defined by their content of NKG2A+/NKG2A- cells, frequency of receptor-null cells, and degree of KIR receptor co-expression. The analyses provide new perspective on how personalized human NK cell repertoires are structured.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
K. Gendzekhadze, P. J. Norman, L. Abi-Rached, T. Graef, A. K. Moesta, Z. Layrisse, and P. Parham
Co-evolution of KIR2DL3 with HLA-C in a human population retaining minimal essential diversity of KIR and HLA class I ligands
PNAS,
November 3, 2009;
106(44):
18692 - 18697.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Graef, A. K. Moesta, P. J. Norman, L. Abi-Rached, L. Vago, A. M. Older Aguilar, M. Gleimer, J. A. Hammond, L. A. Guethlein, D. A. Bushnell, et al.
KIR2DS4 is a product of gene conversion with KIR3DL2 that introduced specificity for HLA-A*11 while diminishing avidity for HLA-C
J. Exp. Med.,
October 26, 2009;
206(11):
2557 - 2572.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. J. Rose, A. G. Brooks, L. A. Stewart, T. H. Nguyen, and A. P. Schwarer
Killer Ig-Like Receptor Ligand Mismatch Directs NK Cell Expansion In Vitro
J. Immunol.,
October 1, 2009;
183(7):
4502 - 4508.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Andersson, C. Fauriat, J.-A. Malmberg, H.-G. Ljunggren, and K.-J. Malmberg
KIR acquisition probabilities are independent of self-HLA class I ligands and increase with cellular KIR expression
Blood,
July 2, 2009;
114(1):
95 - 104.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. J. Norman, L. Abi-Rached, K. Gendzekhadze, J. A. Hammond, A. K. Moesta, D. Sharma, T. Graef, K. L. McQueen, L. A. Guethlein, C. V.F. Carrington, et al.
Meiotic recombination generates rich diversity in NK cell receptor genes, alleles, and haplotypes
Genome Res.,
May 1, 2009;
19(5):
757 - 769.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Yu, J. M. Venstrom, X.-R. Liu, J. Pring, R. S. Hasan, R. J. O'Reilly, and K. C. Hsu
Breaking tolerance to self, circulating natural killer cells expressing inhibitory KIR for non-self HLA exhibit effector function after T cell-depleted allogeneic hematopoietic cell transplantation
Blood,
April 16, 2009;
113(16):
3875 - 3884.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. T. Joncker, N. C. Fernandez, E. Treiner, E. Vivier, and D. H. Raulet
NK Cell Responsiveness Is Tuned Commensurate with the Number of Inhibitory Receptors for Self-MHC Class I: The Rheostat Model
J. Immunol.,
April 15, 2009;
182(8):
4572 - 4580.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Brodin, T. Lakshmikanth, S. Johansson, K. Karre, and P. Hoglund
The strength of inhibitory input during education quantitatively tunes the functional responsiveness of individual natural killer cells
Blood,
March 12, 2009;
113(11):
2434 - 2441.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Fauriat, S. Andersson, A. T. Bjorklund, M. Carlsten, M. Schaffer, N. K. Bjorkstrom, B. C. Baumann, J. Michaelsson, H.-G. Ljunggren, and K.-J. Malmberg
Estimation of the Size of the Alloreactive NK Cell Repertoire: Studies in Individuals Homozygous for the Group A KIR Haplotype
J. Immunol.,
November 1, 2008;
181(9):
6010 - 6019.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Sanjanwala, M. Draghi, P. J. Norman, L. A. Guethlein, and P. Parham
Polymorphic Sites Away from the Bw4 Epitope That Affect Interaction of Bw4+ HLA-B with KIR3DL1
J. Immunol.,
November 1, 2008;
181(9):
6293 - 6300.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. N. Bimber, A. J. Moreland, R. W. Wiseman, A. L. Hughes, and D. H. O'Connor
Complete Characterization of Killer Ig-Like Receptor (KIR) Haplotypes in Mauritian Cynomolgus Macaques: Novel Insights into Nonhuman Primate KIR Gene Content and Organization
J. Immunol.,
November 1, 2008;
181(9):
6301 - 6308.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
