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Effect of anH-2 mutation on cytotoxic T cell recognition. Specific antigen can determine the pattern ofH-2 restriction
Authors:James Forman
Institution:(1) Department of Microbiology, University of Texas Health Science Center at Dallas, 5323 Harry Hines Boulevard, 75235 Dallas, Texas
Abstract:Hz1 (H-2 bm1 ) mice, an H-2 mutant strain derived from C57BL/6(H-2 b ), were either injected with vaccinia virus or had their spleen cells sensitized in vitro with syngeneic TNP-modified cells. The cytotoxic cells generated were tested for their activity against target cells that were either infected with vaccinia virus, TNP-modified, or both vaccinia infected and TNP-modified.Hz1 anti-TNP cytotoxic cells specifically lysed syngeneic target cells that were trinitrophenylated but not infected with vaccinia virus, while anti-vaccinia cells specifically lysed vaccinia infected target cells but not TNP-cells. Hz1 (H-2K bm1 D b ) anti-TNP effector cells killed B10.A(5R)-TNP (H-2K b D d ) targets, indicating that there is cross-reactivity between TNP-H-2Kb and TNP-H-2Kbm1. On the other hand, there is no cross-reactivity between vaccinia-H-2Kb and H-2Kbm1, since Hz1 anti-vaccinia effector cells did not kill vaccinia infected B10.A(5R) targets.Since Hz1 anti-TNP effector cells lysed B10.A(5R) target cells that were first infected with vaccinia virus and then derivatized with TNP, virus does not mask cross-reactive determinants shared by TNP-H-2Kb and H-2Kbm1. Additional experiments showed that Hz1 anti-TNP effector cells lysed TNP-modified and vaccinia infected B10.A(5R) target cells irrespective of the virus concentration used for infection or the time of addition of virus. Further, there are no detectable quantitative differences between C57BL/6 and Hz1 anti-TNP effector cells in their ability to kill TNP-5R targets.The cytotoxic effect of Hz1 anti-TNP effector cells on B10.A(5R)-TNP targets could not be blocked with TNP derivatized inhibitor cells that carry theH-2D d region allele. Thus, the ability of anti-TNP H-2Kb effector cells to cross-react with H-2Kbm1 cannot be explained by a cross-reaction between H-2Kbm1 and H-2Dd.Abbreviations used in this paper TNP trinitrophenol - PFU plaque forming unit - Con A Concanavalin A - BSS balanced-salt-solution - FCS fetal calf serum - TNBS trinitrobenzene sulfonic acid - PBS phosphate-buffered-saline
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