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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. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-03-143727v1 112/6/2369    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Yawata, M. Articles by Parham, P. Search for Related Content PubMed PubMed Citation Articles by Yawata, M. Articles by Parham, P. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY MHC class I–specific inhibitory receptors and their ligands structure diverse human NK-cell repertoires toward a balance of missing self-response Makoto Yawata1,*, Nobuyo Yawata1,*, Monia Draghi1, Fotini Partheniou2, Ann-Margaret Little2,3, and Peter Parham1 1 Department of Structural Biology, Stanford University School of Medicine, CA; 2 Histocompatibility Laboratories, Anthony Nolan Trust, and 3 Department of Haematology, the Royal Free Hospital, London, United Kingdom Variegated expression of 6 inhibitory HLA class I–specific receptors on primary NK cells was studied using high-dimension flow cytometry in 58 humans to understand the structure and function of NK-cell repertoires. Sixty-four subsets expressing all possible receptor com-binations were present in each repertoire, and the frequency of receptor-null cells varied among 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 that 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, 5 types of NK-cell repertoire were defined by their content of NKG2A+/NKG2A– cells, frequency of receptor-null cells, and degree of KIR receptor coexpression. 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: 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]

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