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Stochastic acquisition of Qa1 receptors during the development of fetal NK cells in vitro accounts in part but not in whole for the ability of these cells to distinguish between class I-sufficient and class I-deficient targets.
J Immunol. 1999 Sep 15; 163(6):3176-84.JI

Abstract

Fetal mouse NK cells are grossly deficient in the expression of Ly49 molecules yet show a limited ability to distinguish between wild-type and MHC class I-deficient target cells. In this paper we report that during their development in vitro from immature thymic progenitors, a proportion of C57BL/6 fetal NK cells acquires receptors for a soluble form of the nonclassical class I molecule Qa1b associated with the Qdm peptide, but not for soluble forms of the classical class I molecules Kb and Db. The acquisition of these Qa1 receptors occurs in a stochastic manner that is strictly controlled by cytokines, and in particular is strongly inhibited by IL-4. All fetal NK clones tested, including those that lack detectable Qa1 receptors, express mRNA for CD94 and for both inhibitory and noninhibitory members of the NKG2 family. Fetal NK cells lacking receptors for Qa1 (and also for classical class I molecules) cannot distinguish between wild-type and class I-deficient blasts but, surprisingly, distinguish efficiently between certain wild-type and class I-deficient tumor cells. A variant line that lacks several members of the NKG2 family kills both types of tumor cell equally well, suggesting the existence of NKG2-containing inhibitory receptors that recognize as yet undefined nonclassical class I molecules of restricted distribution.

Authors+Show Affiliations

Department of Microbiology and Immunology, The Medical School, Newcastle, United Kingdom.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10477585

Citation

Toomey, J A., et al. "Stochastic Acquisition of Qa1 Receptors During the Development of Fetal NK Cells in Vitro Accounts in Part but Not in Whole for the Ability of These Cells to Distinguish Between Class I-sufficient and Class I-deficient Targets." Journal of Immunology (Baltimore, Md. : 1950), vol. 163, no. 6, 1999, pp. 3176-84.
Toomey JA, Salcedo M, Cotterill LA, et al. Stochastic acquisition of Qa1 receptors during the development of fetal NK cells in vitro accounts in part but not in whole for the ability of these cells to distinguish between class I-sufficient and class I-deficient targets. J Immunol. 1999;163(6):3176-84.
Toomey, J. A., Salcedo, M., Cotterill, L. A., Millrain, M. M., Chrzanowska-Lightowlers, Z., Lawry, J., Fraser, K., Gays, F., Robinson, J. H., Shrestha, S., Dyson, P. J., & Brooks, C. G. (1999). Stochastic acquisition of Qa1 receptors during the development of fetal NK cells in vitro accounts in part but not in whole for the ability of these cells to distinguish between class I-sufficient and class I-deficient targets. Journal of Immunology (Baltimore, Md. : 1950), 163(6), 3176-84.
Toomey JA, et al. Stochastic Acquisition of Qa1 Receptors During the Development of Fetal NK Cells in Vitro Accounts in Part but Not in Whole for the Ability of These Cells to Distinguish Between Class I-sufficient and Class I-deficient Targets. J Immunol. 1999 Sep 15;163(6):3176-84. PubMed PMID: 10477585.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Stochastic acquisition of Qa1 receptors during the development of fetal NK cells in vitro accounts in part but not in whole for the ability of these cells to distinguish between class I-sufficient and class I-deficient targets. AU - Toomey,J A, AU - Salcedo,M, AU - Cotterill,L A, AU - Millrain,M M, AU - Chrzanowska-Lightowlers,Z, AU - Lawry,J, AU - Fraser,K, AU - Gays,F, AU - Robinson,J H, AU - Shrestha,S, AU - Dyson,P J, AU - Brooks,C G, PY - 1999/9/8/pubmed PY - 1999/9/8/medline PY - 1999/9/8/entrez SP - 3176 EP - 84 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 163 IS - 6 N2 - Fetal mouse NK cells are grossly deficient in the expression of Ly49 molecules yet show a limited ability to distinguish between wild-type and MHC class I-deficient target cells. In this paper we report that during their development in vitro from immature thymic progenitors, a proportion of C57BL/6 fetal NK cells acquires receptors for a soluble form of the nonclassical class I molecule Qa1b associated with the Qdm peptide, but not for soluble forms of the classical class I molecules Kb and Db. The acquisition of these Qa1 receptors occurs in a stochastic manner that is strictly controlled by cytokines, and in particular is strongly inhibited by IL-4. All fetal NK clones tested, including those that lack detectable Qa1 receptors, express mRNA for CD94 and for both inhibitory and noninhibitory members of the NKG2 family. Fetal NK cells lacking receptors for Qa1 (and also for classical class I molecules) cannot distinguish between wild-type and class I-deficient blasts but, surprisingly, distinguish efficiently between certain wild-type and class I-deficient tumor cells. A variant line that lacks several members of the NKG2 family kills both types of tumor cell equally well, suggesting the existence of NKG2-containing inhibitory receptors that recognize as yet undefined nonclassical class I molecules of restricted distribution. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/10477585/Stochastic_acquisition_of_Qa1_receptors_during_the_development_of_fetal_NK_cells_in_vitro_accounts_in_part_but_not_in_whole_for_the_ability_of_these_cells_to_distinguish_between_class_I_sufficient_and_class_I_deficient_targets_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=10477585 DB - PRIME DP - Unbound Medicine ER -