Mak Lab

Molecular Immunology


Makrigiannis lab trainees are underlined


58.NKR-P1B expression in gut-associated innate lymphoid cells is required for the control of gastrointestinal tract infections.

Abou-Samra E, Hickey Z, Aguilar OA, Scur M, Mahmoud AB, Pyatibrat S, Tu MM, Francispillai J, Mortha A, Carlyle JR, Rahim MMA, Makrigiannis AP.

Cell Mol Immunol. 2018 Oct 1. doi: 10.1038/s41423-018-0169-x. [Epub ahead of print]




70Critical role for the Ly49 family of class I MHC receptors in adaptive natural killer cell responses.

Wight A, Mahmoud AB, Scur M, Tu MM, Rahim MMA, Sad S, Makrigiannis AP.

Proc Natl Acad Sci U S A. 2018 Nov 6;115(45):11579-11584. doi: 10.1073/pnas.1722374115. Epub 2018 Sep 24.




69 The ITIM Domain-Containing NK Receptor Ly49Q Impacts Pulmonary Infection by Mediating Neutrophil Functions.

Margraf A, Volmering S, Skupski J, Van Marck V, Makrigiannis AP, Block H, Zarbock A.

J Immunol. 2018 Jun 15;200(12):4085-4093. doi: 10.4049/jimmunol.1701084. Epub 2018 Apr 30.





Immunosurveillance and Immunoediting of Breast Cancer via Class I MHC Receptors.

Tu MM, Rahim MMA, Sayed C, Mahmoud AB, Makrigiannis AP.

Cancer Immunol Res. 2017 Nov;5(11):1016-1028. doi: 10.1158/2326-6066.CIR-17-0056. Epub 2017 Sep 18.

Aguilar OA, Berry R, Rahim MMA, Reichel JJ, Popović B, Tanaka M, Fu Z, Balaji GR, Lau TNH, Tu MM, Kirkham CL, Mahmoud AB, Mesci A, Krmpotić A, Allan DSJ, Makrigiannis AP, Jonjić S, Rossjohn J, Carlyle JR.

Cell. 2017 Mar 23;169(1):58-71.e14. doi: 10.1016/j.cell.2017.03.002.


NK-Cell Recruitment Is Necessary for Eradication of Peritoneal Carcinomatosis with an IL12-Expressing Maraba Virus Cellular Vaccine.

Alkayyal AA, Tai LH, Kennedy MA, de Souza CT, Zhang J, Lefebvre C, Sahi S, Ananth AA, Mahmoud AB, Makrigiannis AP, Cron GO, Macdonald B, Marginean EC, Stojdl DF, Bell JC, Auer RC.

Cancer Immunol Res. 2017 Mar;5(3):211-221. doi: 10.1158/2326-6066.CIR-16-0162. Epub 2017 Feb 3.


Correction: Influenza Virus Targets Class I MHC-Educated NK Cells for Immunoevasion.

Mahmoud AB, Tu MM, Wight A, Zein HS, Rahim MM, Lee SH, Sekhon HS, Brown EG, Makrigiannis AP.

PLoS Pathog. 2016 Nov 4;12(11):e1006021. doi: 10.1371/journal.ppat.1006021. eCollection 2016 Nov. Erratum in: PLoS Pathog. 2016 Dec 16;12 (12 ):e1006105.


Expansion and Protection by a Virus-Specific NK Cell Subset Lacking Expression of the Inhibitory NKR-P1B Receptor during Murine Cytomegalovirus Infection.

Rahim MM, Wight A, Mahmoud AB, Aguilar OA, Lee SH, Vidal SM, Carlyle JR, Makrigiannis AP.

J Immunol. 2016 Sep 15;197(6):2325-37. doi: 10.4049/jimmunol.1600776. Epub 2016 Aug 10.


Licensed and Unlicensed NK Cells: Differential Roles in Cancer and Viral Control.

Tu MM, Mahmoud AB, Makrigiannis AP.

Front Immunol. 2016 May 2;7:166. doi: 10.3389/fimmu.2016.00166. eCollection 2016. Review.


Nucleosome Presence at AML-1 Binding Sites Inversely Correlates with Ly49 Expression: Revelations from an Informatics Analysis of Nucleosomes and Immune Cell Transcription Factors.

Wight A, Yang D, Ioshikhes I, Makrigiannis AP.

PLoS Comput Biol. 2016 Apr 28;12(4):e1004894. doi: 10.1371/journal.pcbi.1004894. eCollection 2016 Apr.


Ly49 knockdown in mice results in aberrant uterine crypt formation and impaired blastocyst implantation.

Leon L, Felker AM, Kay VR, Tu MM, Makrigiannis AP, Croy BA.

Placenta. 2016 Mar;39:147-50. doi: 10.1016/j.placenta.2016.01.013. Epub 2016 Jan 26.


Influenza Virus Targets Class I MHC-Educated NK Cells for Immunoevasion.

Mahmoud AB, Tu MM, Wight A, Zein HS, Rahim MM, Lee SH, Sekhon HS, Brown EG, Makrigiannis AP.

PLoS Pathog. 2016 Feb 29;12(2):e1005446. doi: 10.1371/journal.ppat.1005446. eCollection 2016 Feb. Erratum in: PLoS Pathog. 2016 Nov 4;12 (11):e1006021.


Endothelial Gata5 transcription factor regulates blood pressure.

Messaoudi S, He Y, Gutsol A, Wight A, Hébert RL, Vilmundarson RO, Makrigiannis AP, Chalmers J, Hamet P, Tremblay J, McPherson R, Stewart AF, Touyz RM, Nemer M.

Nat Commun. 2015 Nov 30;6:8835. doi: 10.1038/ncomms9835.

58.Rahim MM, Makrigiannis APLy49 receptors: evolution, genetic diversity, and impact on immunity. Immunol Rev. 2015 Sep;267(1):137-47. doi: 10.1111/imr.12318. Review.

57. Chen P, Aguilar OA, Rahim MM, Allan DS, Fine JH, Kirkham CL, Ma J, Tanaka M, Tu MM, Wight A, Kartsogiannis V, Gillespie MT, Makrigiannis AP, Carlyle JR. Genetic Investigation of MHC-Independent Missing-Self Recognition by Mouse NK Cells Using an In Vivo Bone Marrow Transplantation Model.J Immunol. 2015 Mar 15;194(6):2909-18. doi: 10.4049/jimmunol.1401523. Epub 2015 Feb 13.


The mouse NKR-P1B:Clr-b recognition system is a negative regulator of innate immune responses.


Rahim MM, Chen P, Mottashed AN, Mahmoud AB, Thomas MJ, Zhu Q, Brooks CG, Kartsogiannis V, Gillespie MT, Carlyle JR, Makrigiannis AP.

Blood. 2015 Apr 2;125(14):2217-27. doi: 10.1182/blood-2014-02-556142. Epub 2015 Jan 22.





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55. Wei H, Nash WT, Makrigiannis AP, Brown MG. Impaired NK-cell education diminishes resistance to murine CMV infection.Eur J Immunol. 2014 Sep 3. doi: 10.1002/eji.201444800. Epub 2014 Oct 1.

54. Lima PD, Tu MM, Rahim MM, Peng AR, Anne Croy B, Makrigiannis AP. Ly49 receptors activate angiogenic mouse DBA+ uterine natural killer cells. Cell Mol Immunol. 2014 Sep;11(5):467-476. doi: 10.1038/cmi.2014.44. Epub 2014 Jun 23.

53. Tu MM, Mahmoud AB, Wight A, Mottashed A, Bélanger S, Rahim MM, Abou-Samra E, Makrigiannis AP. Ly49 family receptors are required for cancer immunosurveillance mediated by natural killer cells. Cancer Res. 2014 Jul 15;74(14):3684-94. doi: 10.1158/0008-5472.CAN-13-3021. Epub 2014 May 6.

52. Klingel K, Fabritius C, Sauter M, Göldner K, Stauch D, Kandolf R, Ettischer N, Gahlen S, Schönberger T, Ebner S, Makrigiannis AP, Bélanger S, Diefenbach A, Polić B, Pratschke J, Kotsch K. The activating receptor NKG2D of natural killer cells promotes resistance against enterovirus-mediated inflammatory cardiomyopathy. J Pathol. 2014 Oct;234(2):164-77. doi: 10.1002/path.4369. Epub 2014 Aug 6.

51. Rahim MM, Tu MM, Mahmoud AB, Wight A, Abou-Samra E, Lima PD, Makrigiannis AP. Ly49 receptors: innate and adaptive immune paradigms. Front Immunol. 2014 Apr 2;5:145. doi: 10.3389/fimmu.2014.00145. eCollection 2014. Review.

50. Zhang J, Tai LH, Ilkow CS, Alkayyal AA, Ananth AA, de Souza CT, Wang J, Sahi S, Ly L, Lefebvre C, Falls TJ, Stephenson KB, Mahmoud AB, Makrigiannis AP, Lichty BD, Bell JC, Stojdl DF, Auer RC. Maraba MG1 virus enhances natural killer cell function via conventional dendritic cells to reduce postoperative metastatic disease. Mol Ther. 2014 Jul;22(7):1320-32. doi: 10.1038/mt.2014.60. Epub 2014 Apr 3.

49. McFall E, Tu MM, Al-Khattabi N, Tai LH, St-Laurent AS, Tzankova V, Hall CW, Belanger S, Troke AD, Wight A, Mahmoud AB, Zein HS, Rahim MM, Carlyle JR, Makrigiannis AP. Optimized tetramer analysis reveals Ly49 promiscuity for MHC ligands. J Immunol. 2013 Dec 1;191(11):5722-9. doi: 10.4049/jimmunol.1300726. Epub 2013 Oct 23.

48. Tai LH, Zhang J, Scott KJ, de Souza CT, Alkayyal AA, Ananth AA, Sahi S, Adair RA, Mahmoud AB, Sad S, Bell JC, Makrigiannis AP, Melcher AA, Auer RC. Perioperative influenza vaccination reduces postoperative metastatic disease by reversing surgery-induced dysfunction in natural killer cells. Clin Cancer Res. 2013 Sep 15;19(18):5104-15. doi: 10.1158/1078-0432.CCR-13-0246. Epub 2013 Jul 23.

47. Rahim MM, Tai LH, Troke AD, Mahmoud AB, Abou-Samra E, Roy JG, Mottashed A, Ault N, Corbeil C, Goulet ML, Zein HS, Hamilton-Valensky M, Krystal G, Kerr WG, Toyama-Sorimachi N, Makrigiannis AP. Ly49Q positively regulates type I IFN production by plasmacytoid dendritic cells in an immunoreceptor tyrosine-based inhibitory motif-dependent manner. J Immunol. 2013 Apr 15;190(8):3994-4004. doi: 10.4049/jimmunol.1200873. Epub 2013 Mar 11.

46. Zhang Q, Rahim MM, Allan DS, Tu MM, Belanger S, Abou-Samra E, Ma J, Sekhon HS, Fairhead T, Zein HS, Carlyle JR, Anderson SK, Makrigiannis AP. Mouse Nkrp1-Clr gene cluster sequence and expression analyses reveal conservation of tissue-specific MHC-independent immunosurveillance. PLoS One. 2012;7(12):e50561. doi: 10.1371/journal.pone.0050561. Epub 2012 Dec 4.

45. Tai LH, de Souza CT, Bélanger S, Ly L, Alkayyal AA, Zhang J, Rintoul JL, Ananth AA, Lam T, Breitbach CJ, Falls TJ, Kirn DH, Bell JC, Makrigiannis AP, Auer RA. Preventing postoperative metastatic disease by inhibiting surgery-induced dysfunction in natural killer cells. Cancer Res. 2013 Jan 1;73(1):97-107. doi: 10.1158/0008-5472.CAN-12-1993. Epub 2012 Oct 22.

44. Bélanger S, Tu MM, Rahim MM, Mahmoud AB, Patel R, Tai LH, Troke AD, Wilhelm BT, Landry JR, Zhu Q, Tung KS, Raulet DH, Makrigiannis AP.Impaired natural killer cell self-education and “missing-self” responses in Ly49-deficient mice.Blood. 2012 Jul 19;120(3):592-602. Epub 2012 Jun 1.

43. Heyward CY, Patel R, Mace EM, Grier JT, Guan H, Makrigiannis AP, Orange JS, Ricciardi RP. Immunol Lett. 2012 May 30;144(1-2):16-23. doi: 10.1016/j.imlet.2012.03.001. Epub 2012 Mar 14.Tumorigenic adenovirus 12 cells evade NK cell lysis by reducing the expression of NKG2D ligands.

42. Chen P*, Bélanger S*, AguilarOA, Zhang Q, St.-Laurent A, Ahmed Rahim MM, Makrigiannis AP*, and Carlyle JR*.Analysis of the mouse 129-strain Nkrp1-Clr gene cluster reveals conservation of genomic organization and functional receptor-ligand interactions despite significant allelic polymorphism.Immunogenetics. 2011; 63:627-40. *denotes equal contribution.

41. Patel R, Bélanger S, Tai L-H, Troke AD, and Makrigiannis AP. Effect of Ly49 haplotype variance on natural killer cell function and education. J. Immunol. 2010; 185:4783-92.

40. Xie X, Stadnisky MD, Coats ER, Ahmed Rahim MM, Lundgren A, Xu W, Makrigiannis AP, and Brown MG. MHC class I Dk expression in hematopoietic and nonhematopoietic cells confers natural killer cell resistance to murine cytomegalovirus. PNAS.2010; 107:8754-9.

39. Hayashi M, Nakashima T, Kodama T, Makrigiannis AP, Toyama-Sorimachi N, and Takayanagi H.Ly49Q, an ITIM-bearing NK receptor, positively regulates osteoclast differentiation. Biochem. Biophys. Res. Comm.2010; 393:432-8.

38. Sasawatari S, Yoshizaki M, Taya C, Tazawa A, Furuyama-Tanaka K, Yonekawa H, Dohi T,Makrigiannis AP, Sasazuki T, Inaba K, and Toyama-Sorimachi N. The Ly49Q receptor plays a crucial role in neutrophil polarization and migration by regulating raft trafficking. Immunity. 2010; 32:200-13.

37. Yoshizaki M, Tazawa A, Kasumi E, Sasawatari S, Itoh K, Dohi T, Sasazuki T, Inaba K, Makrigiannis AP, and Toyama-Sorimachi N. Spatiotemporal regulation of intracellular trafficking of TLR9 by an inhibitory receptor, Ly49Q. Blood. 2009; 114:1518-27.

36. Makrigiannis AP and Parham P. The evolution of NK cell diversity. Semin. Immunol. 2008; 20:309-10 (Editorial).

35. Carlyle JR, Mesci A, Fine JH, Chen P, Bélanger S, Tai L-H, and Makrigiannis AP. Evolution of the Ly49 and Nkrp1 recognition systems. Semin. Immunol. 2008; 20:321-30 (Invited review).

34. Tai L-H, Goulet M-L, Bélanger S, Toyama-Sorimachi N, Fodil-Cornu N, Vidal SM, Troke AD, McVicar DW, and Makrigiannis AP. Positive regulation of plasmacytoid dendritic cell function via Ly49Q recognition of class I MHC. J. Exp. Med. 2008; 205:3187-99.

33. Fodil-Cornu N, Lee S-H, Bélanger S, Makrigiannis AP, Biron CA, Buller MR and Vidal SM. Ly49h deficient C57BL/6 mice: a new MCMV susceptible model remains resistant to unrelated pathogens controlled by the Natural Killer gene Complex. J. Immunol.2008; 181:6394-6405.

32. Bélanger S, Tai L-H, Anderson SK, and Makrigiannis AP. Ly49 cluster sequence analysis in a mouse model of diabetes: A surplus of activating Ly49 in the NOD genome. Genes Immun. 2008; 9:509-21. (Featured article)

31. Colina R, Costa-Mattioli M, Dowling RJO, Tai L-H, Jaramillo M, Breitbach CJ, Martineau Y, Larsson O, Rong L, Svitki YV, Makrigiannis AP, Bell JC, and Sonenberg N. Translational control of the innate immune response via IRF-7. Nature. 2008; 452:323-8.

30. Tai L-H, Goulet M-L, Bélanger S,Troke AD, St-Laurent AG, Mesci A, Toyama-Sorimachi N, Carlyle JR and Makrigiannis AP. Recognition of H-2Kb by Ly49Q suggests a role for class Ia MHC regulation of plasmacytoid dendritic cell function. Mol. Immunol.2007; 44:2638-46.

29. Mesci A, Ljutic B, Makrigiannis AP and Carlyle JR. NKR-P1 biology: from prototype to missing self (review). Immunol. Res.2006; 35:13-26.

28. Carlyle JR, Mesci A, Ljutic B, Bélanger S, Tai L-H, Rousselle E, Troke AD, Proteau M-F andMakrigiannis AP. Molecular and genetic basis for strain-dependent NK1.1 alloreactivity of mouse NK cells. J. Immunol. 2006; 176:7511-24.

27. Anderson SK, Dewar K, Goulet ML, Leveque G and Makrigiannis AP. Complete elucidation of a minimal class I MHC natural killer cell receptor haplotype. Genes Immun. 2005; 6:481-492 (Featured article).

26. Desrosiers MP, Kielczewska A, Girard-Adam S, Makrigiannis AP, Lemieux S, Morgan K, Loredo-Osti JC, Pham T, Lodoen MB, Lanier LL and Vidal, SM. Epistasis between mouse Klra and major histocompatibility complex class I loci is associated with a new mechanism of natural killer cell-mediated innate resistance to cytomegalovirus infection. Nat. Genet. 2005; 37:593-9.

25. Makrigiannis AP, Patel D, Goulet ML, Dewar K and Anderson SK. Direct Sequence comparison of two divergent class I MHC natural killer cell receptor haplotypes: implications for the evolution of the Ly49gene family. Genes Immun.2005; 6:71-83.

24. Proteau MF, Rousselle E, Makrigiannis AP. Mapping of the BALB/c Ly49 Cluster Defines a Minimal Natural Killer Cell Receptor Gene Repertoire. Genomics.2004; 84:669-677.

23. Makrigiannis AP, Rousselle E, Anderson SK. Independent control of Ly49g alleles: implications for repertoire selection and tumor cell killing. J. Immunol.2004; 172:1414-25.

22. Makrigiannis AP, Anderson SK. Regulation of natural killer cell function (review). Cancer Biol. Ther.2003; 2:610-6.

21. McVicar DW, Winkler-Pickett R, Taylor LS, Makrigiannis AP, Bennett M, Anderson SK, Ortaldo JR. Aberrant Dap12 signaling in the 129 strain of mice: implications for the analysis of gene targeted mice. J. Immunol. 2002; 169:1721-28.

20. Saleh A, Makrigiannis AP, Hodge DL, Anderson SK. Identification of a novel Ly49 promoter that is active in bone marrow and fetal thymus. J. Immunol.2002; 168:5163-69.

19. Makrigiannis AP, Pau AT, Schwartzberg PL, McVicar DW, Beck TW, Anderson SK. A BAC contig map of the Ly49 gene cluster in 129 mice reveals extensive differences in gene content relative to C57BL/6 mice. Genomics.2002; 79:437-444.

18. Makrigiannis AP, Pau AT, Saleh A, Winkler-Pickett R, Ortaldo JR, Anderson SK. Class I MHC binding characteristics of the 129/J Ly49 repertoire. J. Immunol.2001; 166:5034-5043.

17. Makrigiannis AP, Musgrave BL, Haeryfar SMM, Hoskin DW. Interleukin-12 can replace CD28-dependent T cell costimulation during non specific cytotoxic T lymphocyte induction by anti-CD3 antibody. J. Leukoc. Biol.2001; 69:113-122.

16. Makrigiannis AP, Anderson SK. Mechanisms controlling the expression and diversity of the Ly49 gene family (review). Mod. Asp. Immunobiol.2001; 1:228-232.

15. Makrigiannis AP, Anderson SK. The murine Ly49 family: form and function (review). Arch. Immunol. Ther. Exp. 2001; 49:47-50.

14. Makrigiannis AP, Etzler J, Winkler-Pickett R, Mason A, Ortaldo JR, Anderson SK. Identification of the Ly49L protein: evidence for activating counterparts to inhibitory Ly49 proteins. J. Leukoc. Biol. 2000; 68:765-771.

13. Gosselin P, Makrigiannis AP, Nalewaik R, Anderson SK. Characterization of the Ly49I promoter.Immunogenetics2000; 51:326-331.

12. Makrigiannis AP, Anderson SK. Ly49 gene expression in different inbred mouse strains (review).Immunol. Res.2000; 21:39-47.

11. Makrigiannis AP, Musgrave BL, Hoskin DW. Differential effects of B7-1 and B7-2 on the costimulation of mouse nonspecific cytotoxic T lymphocyte development in response to anti-CD3 antibody. J Leukoc Biol. 1999 Nov;66(5):792-802.

10. Makrigiannis AP, Gosselin P, Mason LH, Taylor LS, McVicar DW, Ortaldo JR, and Anderson SK. Cloning and characterization of a novel activating Ly49 closely related to Ly49A. J. Immunol. 1999; 163:4931-4938.

9. Musgrave BL, Phu T, Butler JJ, Makrigiannis AP, Hoskin DW. Murine TRAIL (TNF-related apoptosis inducing ligand) expression induced by T cell activation is blocked by rapamycin, cyclosporin A and inhibitors of phosphatidylinositol 3-kinase, protein kinase C, and protein tyrosine kinases: evidence for trail induction via the T cell receptor signalling pathway. Exp. Cell Res.1999; 252:96-103.

8. Hoskin DW, Williams B, Fitzpatrick L, Makrigiannis AP. Cell biology and possible therapeutic applications of anti-CD3-activated killer-T cells (review). Int. J. Mol. Med. 1998; 1:893-902.

7. Hoskin DW, Taylor RM, Makrigiannis AP, James H, Lee TD. Dose-dependent enhancing and inhibitory effects of A77 1726 (leflunomide) on cytotoxic T lymphocyte induction. Int. J. Immunopharmacol.1998; 20:505-513.5.

6. Greene AL, Makrigiannis AP, Fitzpatrick L, Hoskin DW. Anti-CD3-activated killer T cells: interleukin-6 modulates the induction of major histocompatibility complex-unrestricted cytotoxicity and the expression of genes coding for cytotoxic effector moleculesJ. Interferon Cytokine Res.1997; 17:727-737.

5. Makrigiannis AP, Hoskin DW. Inhibition of cytotoxic T lymphocyte induction by rapamycin: interleukin-2 rescues granzyme B and perforin expression but only partially restores cytotoxic activity. J. Immunol.1997; 159:4700-4707.

4. Williams BA, Makrigiannis AP, Blay J, Hoskin DW. Treatment of the P815 murine mastocytoma with cisplatin or etoposide upregulates cell-surface Fas (CD95) expression and increases sensitivity to anti-Fas antibody-mediated cytotoxicity and to lysis by anti-CD3-activated killer T-cells. Int. J. Cancer1997; 73:416-423.

3. Hoskin DW, Phu T, Makrigiannis AP. Pentoxifylline inhibits granzyme B and perforin expression following T lymphocyte activation by anti-CD3 antibody. Int. J. Immunopharmacol. 1996; 18:623-631.

2. Fitzpatrick L, Makrigiannis AP, Kaiser M, Hoskin DW. Anti-CD3-activated killer T cells: Interferon-gamma and interleukin-10 cross-regulate granzyme B expression and the induction of major histocompatibility complex-unrestricted cytotoxicity. J. Interferon Cytokine Res.1996; 16:537-546.

1. Makrigiannis AP, Blay J, Hoskin DW. Cyclosporin A inhibits 2-chloroadenosine-induced DNA cleavage in mouse thymocytes. Int. J. Immunopharmacol. 1994; 16:995-1001.