The Journal of Immunology, Vol 147, Issue 6 1765-1772, Copyright © 1991 by American Association of Immunologists

ARTICLES

Alloreactive cytotoxic T cells recognize MHC class I antigen without peptide specificity

A Mullbacher, AB Hill, RV Blanden, WB Cowden, NJ King and RT Hla
Division of Cell Biology, John Curtin School of Medical Research, Australian National University, Canberra.

In this report, experiments are described to differentiate between three potential models of class I MHC allorecognition, namely 1) recognition of peptide-free MHC, 2) peptide-MHC-specific recognition, and 3) peptide-MHC-nonspecific recognition. Using a nucleoprotein peptide (NPP) with a sequence derived from influenza virus nucleoprotein with high affinity for Kd class I MHC molecules, it is shown that target cells rapidly become lysable by Kd-NPP self- restricted cytotoxic T (Tc) cells, and retain sufficient Kd-NPP complexes for at least 72 h. Kd-specific alloreactive Tc cells at the clonal and polyclonal level do not show decreased lysis of Kd-bearing targets in the continuous long term (48 h) presence of NPP. Kd- stimulator cells modified with NPP are able to induce potent Kd-NPP- specific self-restricted Tc cells, however Kd-NPP stimulator cells do not generate Kd-NPP specific alloreactive Tc cells from CBA and B10.A (5R) mouse strains as tested by limiting dilution split clone experiments. Human cells infected with the vaccinia virus recombinant coding for the murine Kd class I MHC Ag can be lysed by murine Kd- specific alloreactive Tc cells. In addition the rate of reemergence of alloreactive and self-restricted Tc cell epitopes on virally infected target cells that had their cell-surface class I MHC Ag removed is identical. These results are consistent with model 3 namely that the majority of Tc precursor and effector cells recognize class I MHC Ag without peptide specificity.

This article has been cited by other articles:

				M. Alsharifi, M. Regner, R. Blanden, M. Lobigs, E. Lee, A. Koskinen, and A. Mullbacher Exhaustion of Type I Interferon Response following an Acute Viral Infection. J. Immunol., September 1, 2006; 177(5): 3235 - 3241. [Abstract] [Full Text] [PDF]

				A. Mullbacher, M. Lobigs, R. T. Hla, T. Tran, T. Stehle, and M. M. Simon Antigen-Dependent Release of IFN-{gamma} by Cytotoxic T Cells Up-Regulates Fas on Target Cells and Facilitates Exocytosis-Independent Specific Target Cell Lysis J. Immunol., July 1, 2002; 169(1): 145 - 150. [Abstract] [Full Text] [PDF]

				F. Momburg, A. Müllbacher, and M. Lobigs Modulation of Transporter Associated with Antigen Processing (TAP)-Mediated Peptide Import into the Endoplasmic Reticulum by Flavivirus Infection J. Virol., June 15, 2001; 75(12): 5663 - 5671. [Abstract] [Full Text]

				M. Regner, M. Lobigs, R. V. Blanden, P. Milburn, and A. Mullbacher Antiviral Cytotoxic T Cells Cross-Reactively Recognize Disparate Peptide Determinants from Related Viruses but Ignore More Similar Self- and Foreign Determinants J. Immunol., March 15, 2001; 166(6): 3820 - 3828. [Abstract] [Full Text] [PDF]

				M. M. Simon, P. Waring, M. Lobigs, A. Nil, T. Tran, R. T. Hla, S. Chin, and A. Mullbacher Cytotoxic T Cells Specifically Induce Fas on Target Cells, Thereby Facilitating Exocytosis-Independent Induction of Apoptosis J. Immunol., October 1, 2000; 165(7): 3663 - 3672. [Abstract] [Full Text] [PDF]

				A. Mullbacher, P. Waring, R. Tha Hla, T. Tran, S. Chin, T. Stehle, C. Museteanu, and M. M. Simon Granzymes are the essential downstream effector molecules for the control of primary virus infections by cytolytic leukocytes PNAS, November 23, 1999; 96(24): 13950 - 13955. [Abstract] [Full Text] [PDF]

				A. Mullbacher, R. Wallich, R. W. Moyer, and M. M. Simon Poxvirus-Encoded Serpins Do Not Prevent Cytolytic T Cell-Mediated Recovery from Primary Infections J. Immunol., June 15, 1999; 162(12): 7315 - 7321. [Abstract] [Full Text] [PDF]

				J. M. Riberdy, K. J. Flynn, J. Stech, R. G. Webster, J. D. Altman, and P. C. Doherty Protection against a Lethal Avian Influenza A Virus in a Mammalian System J. Virol., February 1, 1999; 73(2): 1453 - 1459. [Abstract] [Full Text]

				Y. Shi, K. D. Smith, and C. T. Lutz TAP-Independent MHC Class I Peptide Antigen Presentation to Alloreactive CTL Is Enhanced by Target Cell Incubation at Subphysiologic Temperatures J. Immunol., May 1, 1998; 160(9): 4305 - 4312. [Abstract] [Full Text] [PDF]

				M. M. Simon, M. Hausmann, T. Tran, K. Ebnet, J. Tschopp, R. ThaHla, and A. Mullbacher In Vitro- and Ex Vivo-derived Cytolytic Leukocytes from Granzyme A × B Double Knockout Mice Are Defective in Granule-mediated Apoptosis but not Lysis of Target Cells J. Exp. Med., November 17, 1997; 186(10): 1781 - 1786. [Abstract] [Full Text] [PDF]

				P. A. Smith, A. Brunmark, M. R. Jackson, and T. A. Potter Peptide-independent Recognition by Alloreactive Cytotoxic T Lymphocytes (CTL) J. Exp. Med., March 17, 1997; 185(6): 1023 - 1034. [Abstract] [Full Text] [PDF]