Immunologic Research

, Volume 29, Issue 1–3, pp 81–92 | Cite as

Qa-1, a nonclassical class I histocompatibility molecule with roles in innate and adaptive immunity

  • Peter E. Jensen
  • Barbara A. Sullivan
  • Lisa M. Reed-Loisel
  • Dominique A. Weber
Immunology at Emory University

Abstract

Qa-1, a nonclassical class I histocompatibility molecule expressed in mice, predominantly assembles with a single nonameric peptide, Qdm, derived from the signal sequence of certain class Ia molecules. The Qa-1/Qdm complex is the primary ligand for CD94/NKG2A inhibitory receptors expressed on a major fraction of natural killer (NK) cells. cells become susceptible to killing by NK cells under conditions where surface expression of the Qa-1/Qdm inhibitory ligand is reduced. The CD94/NKG2 “missingself” recognition system serves as mechanism for removing cells that have abnormalities in the intracellular machinery required for assembly and expression of class I-peptides complexes, as a consequence of viral infection, for example. Despite its highly focused peptide-binding specificity, Qa-1 also has a capacity to act as an antigen-presentation molecule for CD8+ T cells. It appears that a small subpopulation of these T cells undergoes positive selection by interaction with Qa-1 in the thymus, and they maintain their specificity for Qa-1 after maturation. The role of these unusual T cells in adaptive immune responses remains to be defined.

Key Words

Nonclassical histocompatibility molecules Qa-1 Natural killer cell T-cell selection 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Lalanne JL, Transy C, Guerin S, Darche S, Meulien P, Kourilsky P: Expression of class I genes in the major histocompatibility complex: identification of eight distinct mRNAs in DBA/2 mouse liver. Cell 1985;41:469–478.PubMedCrossRefGoogle Scholar
  2. 2.
    Transy C, Nash SR, David-Watine B, Cochet M, Hunt SWD, Hood LE, Kourilsky P: A low polymorphic mouse H-2 class I gene from the Tla complex is expressed in a broad variety of cell types. J Exp Med 1987;166:341–361.PubMedCrossRefGoogle Scholar
  3. 3.
    Wolf PR, Cook RG: The class I-b molecule Qa-1 forms heterodimers with H-2Ld and a novel 50-kD glycoprotein encoded centromeric to I-E beta PG-657-68. J Exp Med 1995;181:657–668.PubMedCrossRefGoogle Scholar
  4. 4.
    Stanton TH, Boyse EA: A new serologically defined locus, Qa-1, in the Tla-region of the mouse. Immunogenetics 1976;3:525–531.CrossRefGoogle Scholar
  5. 5.
    Stevens C, Flaherty L: Evidence foe antigen presentation by the class Ib molecule, Qa-1. Res Immunol 1996;147:286–290.PubMedCrossRefGoogle Scholar
  6. 6.
    Connolly DJ, Cotterill LA, Hederer RA, Thorpe CJ, Travers PJ, McVey JH, et al.: A cDNA clone encoding the mouse Qa-1 a histocompatibility antigen and proposed structure of the putative peptide binding site. J Immunol 1993;151:6089–6098.PubMedGoogle Scholar
  7. 7.
    Hermel E, Hart AJ, Miller R, Aldrich CJ: CTL and sequence analyses of MHC class 1B antigens Qa1c (H2-T23r) and QaId (H2-T23f). Immunogenetics 1999;49:712–717.PubMedCrossRefGoogle Scholar
  8. 8.
    Bouvier M, Wiley DC: Importance of peptide amino and carboxyl termini to the stability of MHC class I molecules. Science 1994;265:398–402.PubMedCrossRefGoogle Scholar
  9. 9.
    Kastner DL, Rich RR, Shen FW: Qa-1-associated antigens. I. Generation of H-2-nonrestricted cytotoxic T lymphocytes specific for determinants of the Qa-1 region. J Immunol 1979;123:1232–1238.PubMedGoogle Scholar
  10. 10.
    Forman J: H-2 unrestricted cytotoxic T cell activity against antigens controlled by genes in the QA/TLA region. J Immunol 1979;123:2451–2455.PubMedGoogle Scholar
  11. 11.
    Lindahl KF, Hausmann B, Flaherty L: Polymorphism of a Qa-1-associated antigen defined by cytotoxic T cells. I. Qed-1 a and Qed-1 d. Eur J Immunol 1982;12:159–166.PubMedCrossRefGoogle Scholar
  12. 12.
    Aldrich CJ, Rodgers JR, Rich RR: Regulation of Qa-1 expression and determinant modification by an H-2D-linked gene, Qdm. Immunogenet 1988;28:334–344.CrossRefGoogle Scholar
  13. 13.
    Aldrich CJ, DeCloux A, Woods AS, Cotter RJ, Soloski MJ, Forman J: Identification of a Tap-dependent leader peptide recognized by alloreactive T cells specific for a class Ib antigen. Cell 1994;79:649–658.PubMedCrossRefGoogle Scholar
  14. 14.
    DeCloux A, Woods AS, Cotter RJ, Soloski MJ, Forman J: Dominance of a single peptide bound to the class 1(B) molecule, Qa-1b. J Immunol 1997;158:2183–2191.PubMedGoogle Scholar
  15. 15.
    Cotterill LA, Stauss HJ, Millrain MM, Pappin DJ, Rahman D, Canas B, et al.: Qa-1 interaction and T cell recognition of the Qa-1 determinant modifier peptide. Eur J Immunol 1997;27:2123–2132.PubMedCrossRefGoogle Scholar
  16. 16.
    Aldrich CJ, Waltrip R, Hermel E, Attaya M, Lindahl KF, Monaco JJ, Forman J: T cell recognition of QA-1b antigens on cells lacking a functional Tap-2 transporter. J Immunol 1992;149:3773–3777.PubMedGoogle Scholar
  17. 17.
    Lowen LC, Aldrich CJ, Forman J: Analysis of T cell receptors specific for recognition of class IB antigens. J Immunol 1993;151:6155–6165.PubMedGoogle Scholar
  18. 18.
    Vidovic D, Roglic M, McKune K, Guerder S, MacKay C, Dembic Z: Qa-1 restricted recognition of foreign antigen by a gamma delta T-cell hybridoma. Nature 1989;340:646–650.PubMedCrossRefGoogle Scholar
  19. 19.
    Imani F, Soloski MJ: Heat shock proteins can regulate expression of the Tla region-encoded class Ib molecule Qa-1. Proc Natl Acad Sci USA 1991;88:10475–10479.PubMedCrossRefGoogle Scholar
  20. 20.
    Bouwer HG, Lindahl KF, Baldridge JR, Wagner CR, Barry RA, Hinrichs DJ: An H2-T MHC class Ib molecule presents Listeria monocytogenes-derived antigen to immune CD8+ cytotoxic T cells. J Immunol 1994;152:5352–5360.PubMedGoogle Scholar
  21. 21.
    Bouwer HG, Seaman MS, Forman J, Hinrichs DJ: MHC class Ib-restricted cells contribute to antilisterial immunity: evidence for Qa-1b as a key restricting element for Listeria-specific CTLs. J Immunol 1997;159:2795–2801.PubMedGoogle Scholar
  22. 22.
    Bouwer HG, Bai A, Forman J, Gregory SH, Wing EJ, Barry RA, Hinrichs DJ: Listeria monocytogenes-infected hepatocytes are targets of major histocompatibility complex class Ib-restricted antilisterial cytotoxic T lymphocytes. Infect Immun 1998;66:2814–2817.PubMedGoogle Scholar
  23. 23.
    Seaman MS, Perarnau B, Lindahl KF, Lemonnier FA, Forman J: Response to Listeria monocytogenes in mice lacking MHC class Ia molecules. J Immunol 1999;162:5429–5436.PubMedGoogle Scholar
  24. 24.
    Bouwer HG, Barry RA, Hinrichs DJ: Lack of expansion of major histocompatibility complex class Ib-restricted effector cells following recovery from secondary infection with the intracellular pathogen Listeria monocytogenes. Infect Immun 2001;69:2286–2292.PubMedCrossRefGoogle Scholar
  25. 25.
    Lo WF, Ong H, Metcalf ES, Soloski MJ: T cell responses to Gram-negative intracellular bacterial pathogens: a role for CD8+ T cells in immunity to Salmonella infection and the involvement of MHC class Ib molecules. J Immunol 1999;162:5398–5406.PubMedGoogle Scholar
  26. 26.
    Lo WF, Woods AS, DeCloux A, Cotter RJ, Metcalf ES, Soloski MJ: Molecular minicry mediated by MHC class Ib molecules after infection with gram-negative pathogens. Nat Med 2000;6:215–218.PubMedCrossRefGoogle Scholar
  27. 27.
    Soloski MJ, Metcalf ES: The involvement of class Ib molecules in the host response to infection with Salmonella and its relevance to autoimmunity. Microbes Infect 2001;3:1249–1259.PubMedCrossRefGoogle Scholar
  28. 28.
    Davies A, Kalb S, Liang B, Aldrich CJ, Lemonnier FA, Jiang H, et al.: A peptide from heat shock protein 60 is the dominant peptide bound to Qa-1 in the absence of the MHC class 1a leader sequence peptide Qdm. J Immunol 2003;170:5027–5033.PubMedGoogle Scholar
  29. 29.
    Chun T, Aldrich CJ, Baldeon ME, Kawczynski LV, Soloski MJ, Gaskins HR: Constitutive and regulated expression of the class 1B molecule Qa-1 in pancreatic beta cells. Immunology 1998;94:64–71.PubMedCrossRefGoogle Scholar
  30. 30.
    Jiang H, Ware R, Stall A, Flaherty L, Chess L, Pernis B: Murine CD8+ T cells that specifically delete autologous CD4+ T cells expressing V beta 8 TCR: a role of the Qa-1 molecule. Immunity 1995;2:185–194.PubMedCrossRefGoogle Scholar
  31. 31.
    Jiang H, Chess L: The specific regulation of immune responses by CD8+ T cells restricted by the MHC class 1b molecule, Qa-1. Annu Rev Immunol 2000;18:185–216.PubMedCrossRefGoogle Scholar
  32. 32.
    Jiang H, Braunstein NS, Yu B, Winchester R, Chess L: CD8+ T cells control the TH phenotype of MBP-reactive CD4+ T cells in EAE mice. Proc Natl Acad Sci USA 2001;98:6301–6306.PubMedCrossRefGoogle Scholar
  33. 33.
    Noble A, Zhao ZS, Cantor H: Suppression of immune responses by CD8 cells. II. Qa-1 on activated B cells stimulates CD8 cell suppression of T helper 2 responses. PG-566-71. J Immunol 1998;160:566–571.PubMedGoogle Scholar
  34. 34.
    D'Orazio TJ, Mayhew E, Niederkorn JY: Ocular immune privilege promoted by the presentation of peptide on tolerogenic B cells in the spleen. II. Evidence for presentation by Qa-1. J Immunol 2001;166:26–32.PubMedGoogle Scholar
  35. 35.
    Kraft JR, Vance RE, Pohl J, Martin AM, Raulet DH, Jensen PE: Analysis of Qa-1 (b) peptide binding specificity and the capacity of CD94/NKG2A to discriminate between Qa-1-peptide complexes. J Exp Med 2000; 192:613–624.PubMedCrossRefGoogle Scholar
  36. 36.
    Salcedo M, Bousso P, Ljunggren HG, Kourilsky P, Abastado JP: The Qa-1 b molecule binds to a large subpopulation of murine NK cells. Eur J Immunol 1998;28:4356–4361.PubMedCrossRefGoogle Scholar
  37. 37.
    Salcedo M, Colucci F, Dyson PJ, Cotterill LA, Lemonnier FA, Kourilsky P, et al.: Role of Qa-1(b)-binding receptors in the specificity of developing NK cells. Eur J Immunol 2000;30:1094–1101.PubMedCrossRefGoogle Scholar
  38. 38.
    Vance RE, Kraft JR, Altman JD, Jensen PE, Raulet DH: Mouse CD94/NKG2A is a natural killer cell receptor for the nonclassical major histocompatibility complex (MHC) class 1 molecule Qa-1(b). J Exp Med 1998;188:1841–1848.PubMedCrossRefGoogle Scholar
  39. 39.
    Vance RE, Jamieson AM, Raulet DH: Recognition of the class Ib molecule Qa-1 (b) by putative activating receptors CD94/NKG2C and CD94/NKG2E on mouse natural killer cells. J Exp Med 1999;190:1801–1812.PubMedCrossRefGoogle Scholar
  40. 40.
    Moser JM, Gibbs J, Jensen PE, Lukacher AE: CD94-NKG2A receptors regulate antiviral CD8(+) T cell responses. Nat Immunol 2002;3:189–195.PubMedCrossRefGoogle Scholar
  41. 41.
    Miller JD, Peters M, Oran AE, Beresford GW, Harrington L, Boss JM, Altman JD: CD94/NKG2 expression does not inhibit cytotoxic function of lymphocytic choriomeningitis virus-specific CD8+ T cells. J Immunol 2002;169:693–701.PubMedGoogle Scholar
  42. 42.
    McMahon CW, Zajac AJ, Jamieson AM, Corral L, Hammer GE, Ahmed R, Raulet DH: Viral and bacterial infections induce expression of multiple NK cell receptors in responding CD8(+) T cells. J Immunol 2002;169:1444–1452.PubMedGoogle Scholar
  43. 43.
    Meyers JH, Ryu A, Monney L, Nguyen K, Greenfield EA, Freeman GJ, Kuchnoo VK: Cutting edge: CD94/NKG2 is expressed on Th1 but not Th2 cells and costimulates Th1 effector functions. J Immunol 2002;169:5382–5386.PubMedGoogle Scholar
  44. 44.
    Braud VM, Aldemir H, Breart B, Ferlin WG: Expression of CD94-NK G2A inhibitory receptor is restricted to a subset of CD8(+) T cells. Trends Immunol 2003;24:162–164.PubMedCrossRefGoogle Scholar
  45. 45.
    Braud VM, Allan DS, O'Callaghan CA, Soderstrom K, D'Andrea A, Ogg GS, et al.: HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C. Nature 1998;391:795–799.PubMedCrossRefGoogle Scholar
  46. 46.
    Lee N, Llano M, Carretero M, Ishitani A, Navarro F, Lopez-Botet M, Geraghty DE: HLA-E is a major ligand for the natural killer inhibitory receptor CD94/NKG2A. Proc Natl Acad Sci USA 1998;95:5199–5204PubMedCrossRefGoogle Scholar
  47. 47.
    Borrego F, Ulbrecht M, Weiss EH, Coligan JE, Brooks AG: Recognition of human histocompatility leukocyte antigen (HLA)-E complexed with HLA class I signal sequence-derived peptides by CD94/NKG2 confers protection from natural killer cell-mediated lysis. J Exp Med 1998;187:813–818.PubMedCrossRefGoogle Scholar
  48. 48.
    Keck K: Ir-gene control of immunogenicity of insulin and A-chain loop as a carrier determinant. Nature 1975;254:78–79.PubMedCrossRefGoogle Scholar
  49. 49.
    Thayer WP, Kraft JR, Tompkins SM, Moore JCt, Jensen PE: Assessment of the role of determinant selection in genetic control of the immune response to insulin in H-2b mice. J Immunol 1999;163:2549–2554.PubMedGoogle Scholar
  50. 50.
    Jensen PE: Reduction of disulfide bonds during antigen processing: evidence from a thiol-dependent insulin determinant. J Exp Med 1991;174:1121–1130.PubMedCrossRefGoogle Scholar
  51. 51.
    Fink PJ, Bevan MJ: Positive selection of thymocytes. Adv Immunol 1995;59:99–133.PubMedCrossRefGoogle Scholar
  52. 52.
    Fowlkes BJ SE: Positive selection of T cells. Curr Opin Immunol 1995;7:188–195.PubMedCrossRefGoogle Scholar
  53. 53.
    Bendelac A: Positive selection of mouse NK1+T cells by CD1-expressing cortical thymocytes. J Exp Med 1995;182:2091–2096.PubMedCrossRefGoogle Scholar
  54. 54.
    Coles MC, Raulet DH: NK 1.1+T cells in the liver arise in the thymus and are selected by interactions with class I molecules on CD4+CD8+ cells. J Immunol 2000;164:2412–2418.PubMedGoogle Scholar
  55. 55.
    Urdahl KB, Sun JC, Bevan MJ: Positive selection of MHC class Ib-restricted CD8(+) T cells on hematopoietic cells. Nat Immunol 2002;3:772–779.PubMedGoogle Scholar
  56. 56.
    Pacasova R, Martinozzi S, Boulouis HJ, Szpak Y, Ulbrecht M, Sigaux F, et al.: Cell surface detection of HLA-E gene products with a specific monoclonal antibody. J Reprod Immunol 1999;43:195–201.PubMedCrossRefGoogle Scholar
  57. 57.
    Pietra G, Romagnani C, Falco M, Vitale M, Castriconi R, Pende D, et al.: The analysis of the natural killer-like activity of human cytolytic T lymphocytes revealed HLA-E as a novel target for TCR alpha/beta-mediated recognition. Eur J Immunol 2001;31:3687–3693.PubMedCrossRefGoogle Scholar
  58. 58.
    Romagnani C, Pietra G, Falco M, Millo E, Mazzarino P, Biassoni R, et al.: Identification of HLA-E-specific alloreactive T lymphocytes: a cell subset that undergoes preferential expansion in mixed lymphocyte culture and displays a broad cytolytic activity against allogeneic cells. Proc Natl Acad Sci USA 2002;99:11328–11333.PubMedCrossRefGoogle Scholar
  59. 59.
    Garcia P, Llano M, de Heredia AB, Willberg CB, Caparros E, Aparicio P, et al.: Human T cell receptor-mediated recognition of HLA-E. Eur J Immunol 2002;32:936–944.PubMedCrossRefGoogle Scholar
  60. 60.
    Li J, Goldstein I, Glickman-Nir E, Jiang H, Chess L: Induction of TCR V beta-specific CD8+CTLs by TCR V beta-derived peptides bound to HLA-E. J Immunol 2001;167:3800–3808.PubMedGoogle Scholar
  61. 61.
    Heinzel AS, Grotzke JE, Lines RA, Lewinsohn OA, McNabb AL, Streblow DN, et al.: HLA-E-dependent presentation of Mtb-derived antigen to human CD8+T cells. J Exp Med 2002;196:1473–1481.PubMedCrossRefGoogle Scholar
  62. 62.
    Miller JD, Weber DA, Ibegbu C, Pohl J, Altman JD, Jensen PE: Analysis of HLA-E peptide-binding specificity and contact residues in bound peptide required for recognition by CD94/NKG2. J Immunol 2003;171:1369–1375.PubMedGoogle Scholar
  63. 63.
    Braud V, Jones EY, McMichael A: The human major histocompatibility complex class Ib molecule HLA-E binds signal sequence-derived peptides with primary anchor residues at positions 2 and 9. Eur J Immunol 1997;27:1164–1169.PubMedCrossRefGoogle Scholar
  64. 64.
    O'Callaghan CA, Tomo J, Willcos BE, Braud VM, Jakobsen BK, Stuart DI, et al.: Structural features impose tight peptide binding specificity in the nonclassical MHC molecule HLA-E. Mol Cell 1998;1:531–541.PubMedCrossRefGoogle Scholar
  65. 65.
    Karre K, Ljunggren HG, Piontek G, Kiessling R: Selective rejection of H-2-deficient lymphoma variants suggests alternative immune defence strategy. Nature 1986;319:675–678.PubMedCrossRefGoogle Scholar
  66. 66.
    Ljunggren HG, Karre K: In search of the ‘missing self’ MHC molecules and NK cell recognition. Immunol Today 1990;11:237–244.PubMedCrossRefGoogle Scholar
  67. 67.
    Houchins JP, Lanier LL, Niemi EC, Phillips JH, Ryan JC: Natural killer cell cytolytic activity is inhibited by NKG2-A and activated by NKG2-C. J Immunol 1997;158:3603–3609.PubMedGoogle Scholar
  68. 68.
    Lanier LL, Corliss B, Wu J, Phillips JH: Association of DAP 12 with activating CD94/NKG2C NK cell receptors. Immunity 1998;8:693–701.PubMedCrossRefGoogle Scholar
  69. 69.
    Lohwasser S, Kubota A, Salcedo M, Lian RH, Takei F: The non-classical MHC class I molecule Qa-1(b) inhibits classical MHC class I-restricted cytotoxicity of cytotoxic T lymphocytes. Int Immunol 2001;13:321–327.PubMedCrossRefGoogle Scholar
  70. 70.
    Braud VM, Allan DS, Wilson D, McMichael AJ: TAP- and tapasin-dependent HLA-E surface expression correlates with the binding of an MHC class I leader peptide. Curr Biol 1998;8:1–10.PubMedCrossRefGoogle Scholar
  71. 71.
    Le Drean E, Vely F, Olcese L, Cambiaggi A, Guia S, Krystal G, et al.: Inhibition of antigen-induced T cell response and antibody-induced NK cell cytotoxicity by NKG2A: association of NKG2A with SHP-1 and SHP-2 protein-tyrosine phosphatases. Eur J Immunol 1998;28:264–276.PubMedCrossRefGoogle Scholar
  72. 72.
    Noppen C, Schaefer C, Zajac P, Schutz A, Kocher T, Kloth J, et al.: C-type lectin-like receptors in peptidespecific HLA class I-restricted cytotoxic T lymphocytes: differential expression and modulation of effector functions in clones sharing identical TCR structure and epitope specificity. Eur J Immunol 1998;28:1134–1142.PubMedCrossRefGoogle Scholar
  73. 73.
    Speiser DE, Pittet MJ, Valmori D, Dunbar R, Rimoldi D, Lienard D, et al.: In vivo expression of natural killer cell inhibitory receptors by human melanoma-specific cytolytic T lymphocytes. J Exp Med 1999;190:775–782.PubMedCrossRefGoogle Scholar
  74. 74.
    Mingari MC, Ponte M, Bertone S, Schiavetti F, Vitale C, Bellomo R, et al.: HLA class I-specific inhibitory receptors in human T lymphocytes: interleukin 15-induced expression of CD94/NKG2A in sure rantigen- or alloantigen-activated CD8+ T cells. Proc Natl Acad Sci USA 1998;95:1172–1177.PubMedCrossRefGoogle Scholar
  75. 75.
    Gunturi A, Berg RE, Forman J: Preferential survival of CD8 T and NK cells expressing high levels of CD94. J Immunol 2003;170:1737–1745.PubMedGoogle Scholar
  76. 76.
    Michaelsson J, Teixeira de Matos C, Achour A, Lanier LL, Karre K, Soderstrom K: A signal peptide derived from hsp60 binds HLA-E and interferes with CD94/NKG2A recognition. J Exp Med 2002;196:1403–1414.PubMedCrossRefGoogle Scholar
  77. 77.
    Llano M, Lee N, Navarro F, Garcia P, Albar JP, Geraghty DE, Lopez-Botet M: HLA-E-bound peptides influence recognition by inhibitory and triggering CD94/NKG2 receptors: preferential response to an HLA-G-derived nonamer. Eur J Immunol 1998;28:2854–2863.PubMedCrossRefGoogle Scholar
  78. 78.
    Vales-Gomez M, Reyburn HT, Erskine RA, Lopez-Botet M, Strominger JL: Kinetics and peptide dependency of the binding of the inhibitory NK receptor CD94/NKG2A and the activating receptor CD94/NKG2-C to HLA-E. EMBO J 1999;18:4250–4260.PubMedCrossRefGoogle Scholar
  79. 79.
    Brooks AG, Borrego F, Posch PE, Patamawenu A, Scorzelli CJ, Ulbrecht M, et al.: Specific recognition of HLA-E, but not classical, HLA class I molecules by soluble CD94/NKG2A and NK cells. J Immunol 1999;162:305–313.PubMedGoogle Scholar
  80. 80.
    Tomasec P, Braud VM, Rickards C, Powell MB, McSharry BP, Gadola S, et al.: Surface expression of HLA-E, an inhibitor of natural killer cells, enhanced by human cytomegalovirus gpUL40. Science 2000;287:1031.PubMedCrossRefGoogle Scholar
  81. 81.
    Ulbrecht M, Martinozzi S, Gzeschik M, Hengel H, Ellwart JW, Pla M, Weiss EH: Cutting edge: the human cytomegalovirus UL40 gene product contains a ligand for HLA-E and prevents NK cell-mediated lysis. J Immunol 2000;164:5019–5022.PubMedGoogle Scholar
  82. 82.
    Trowsdale J: Genetic and functional relationships between MHC and NK receptor genes. Immunity 2001;15:363–374.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc 2004

Authors and Affiliations

  • Peter E. Jensen
    • 1
  • Barbara A. Sullivan
    • 1
  • Lisa M. Reed-Loisel
    • 1
  • Dominique A. Weber
    • 1
  1. 1.Department of Pathology and Laboratory MedicineEmory University School of MedicineAtlanta

Personalised recommendations