Indira K Mehta

Publications (2)12.61 Total impact

• Source

  Available from: Jonathan W Heusel

  Article: Recognition of a virus-encoded ligand by a natural killer cell activation receptor.

  Hamish R C Smith, Jonathan W Heusel, Indira K Mehta, Sungjin Kim, Brigitte G Dorner, Olga V Naidenko, Koho Iizuka, Hiroshi Furukawa, Diana L Beckman, Jeanette T Pingel, Anthony A Scalzo, Daved H Fremont, Wayne M Yokoyama
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  ABSTRACT: Natural killer (NK) cells express inhibitory and activation receptors that recognize MHC class I-like molecules on target cells. These receptors may be involved in the critical role of NK cells in controlling initial phases of certain viral infections. Indeed, the Ly49H NK cell activation receptor confers in vivo genetic resistance to murine cytomegalovirus (MCMV) infections, but its ligand was previously unknown. Herein, we use heterologous reporter cells to demonstrate that Ly49H recognizes MCMV-infected cells and a ligand encoded by MCMV itself. Exploiting a bioinformatics approach to the MCMV genome, we find at least 11 ORFs for molecules with previously unrecognized features of predicted MHC-like folds and limited MHC sequence homology. We identify one of these, m157, as the ligand for Ly49H. m157 triggers Ly49H-mediated cytotoxicity, and cytokine and chemokine production by freshly isolated NK cells. We hypothesize that the other ORFs with predicted MHC-like folds may be involved in immune evasion or interactions with other NK cell receptors.
  Proceedings of the National Academy of Sciences 07/2002; 99(13):8826-31. · 9.68 Impact Factor
• Article: Ly49A allelic variation and MHC class I specificity

  Indira K. Mehta, Jian Wang, Jacques Roland, David H. Margulies, Wayne M. Yokoyama
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  ABSTRACT: The Ly49 family of natural killer (NK) cell receptors is encoded by a polygenic genetic locus. Allelic forms have been described and their expression appears to be regulated. The best-characterized Ly49 molecule, the C57BL/6 form of Ly49A, is an NK cell inhibitory receptor that binds H2Dd. To determine whether differences between Ly49a alleles may have functional consequences, allelic variants of Ly49a were cloned from several inbred mouse strains. Stable transfectants expressing each Ly49a allelic variant were generated and tested for reactivity with a panel of monoclonal antibodies (mAbs A1, JR9.318, YE1/32, and YE1/48) that recognize the C57BL/6 form of Ly49A. Binding to H2Dd was also assessed using fluorescently labeled H2Dd tetramers. Furthermore, cytotoxicity assays were performed using anti-Ly49A mAb-separated interleukin-2-activated NK cells. We show that despite binding to fluorescently labeled H2Dd tetramers, the Ly49A+ NK cells from representative mouse strains displayed significantly different degrees of inhibition with H2Dd targets. These results can be interpreted in the light of recent structural data on the Ly49A-H2Dd complex. Thus, the Ly49 family displays functionally significant allelic polymorphism which adds to the repertoire of NK cell receptors.
  Immunogenetics 08/2001; 53(7):572-583. · 2.93 Impact Factor