The Journal of Immunology, Vol 143, Issue 10 3117-3124, Copyright © 1989 by American Association of Immunologists

ARTICLES

Analysis of the HLA-Cw3-specific cytotoxic T lymphocyte response of HLA- B7 X human beta 2m double transgenic mice

C Barra, B Perarnau, P Gerlinger, M Lemeur, A Gillet, P Gibier and FA Lemonnier
Centre d'Immunologie INSERM-CNRS de Marseille-Luminy, France.

The cytolytic responses of either normal (non transgenic), HLA-B7 (single transgenic) or HLA-B7 x human beta 2 microglobulin (double transgenic) DBA/2 mice induced by transfected HLA-Cw3 P815 (H-2d) mouse mastocytoma cells were compared, to evaluate whether the expression of an HLA class I molecule in responder mice would favor the emergence of HLA-specific, H-2-unrestricted CTL. Only 8 of 300 HLA-Cw3-specific CTL clones tested could selectively lyse HLA-Cw3-transfected cells in an H- 2-unrestricted manner, all having been isolated after hyperimmunization of double transgenic mice. These clones also lysed HLA-Cw3+ human cells. Unexpectedly, the lysis of the human but not that of the murine HLA-Cw3 cells was inhibited by Ly-2,3-specific mAb. Despite significant expression of HLA-B7 class I molecules on transgenic lymphoid cells, including thymic cells, limiting dilution analysis and comparative study of TCR-alpha and -beta gene rearrangements of the eight isolated clones (which suggested that they all derived from the same CTL precursor) indicated that the frequency of HLA-Cw3-specific H-2 unrestricted cytotoxic T lymphocytes remained low (even in HLA-B7 x human beta 2-microglobulin double transgenic mice). This suggests that coexpression of HLA class I H and L chain in transgenic mice is not the only requirement for significant positive selection of HLA class I- restricted cytotoxic mouse T lymphocytes.

This article has been cited by other articles:

				P.-S. Rohrlich, S. Cardinaud, H. Firat, M. Lamari, P. Briand, N. Escriou, and F. A. Lemonnier HLA-B*0702 transgenic, H-2KbDb double-knockout mice: phenotypical and functional characterization in response to influenza virus Int. Immunol., June 1, 2003; 15(6): 765 - 772. [Abstract] [Full Text] [PDF]

				A. Sharland, A. Patel, J. H. Lee, A. E. Cestra, S. Saidman, and G. L. Waneck Genetically Modified HLA Class I Molecules Able to Inhibit Human NK Cells Without Provoking Alloreactive CD8+ CTLs J. Immunol., April 1, 2002; 168(7): 3266 - 3274. [Abstract] [Full Text] [PDF]

				S. H. Borenstein, J. Graham, X.-L. Zhang, and J. W. Chamberlain CD8+ T Cells Are Necessary for Recognition of Allelic, But Not Locus-Mismatched or Xeno-, HLA Class I Transplantation Antigens J. Immunol., September 1, 2000; 165(5): 2341 - 2353. [Abstract] [Full Text] [PDF]

				A. Ureta-Vidal, H. Firat, B. Perarnau, and F. A. Lemonnier Phenotypical and Functional Characterization of the CD8+ T Cell Repertoire of HLA-A2.1 Transgenic, H-2Kb{degrees}Db{degrees} Double Knockout Mice J. Immunol., September 1, 1999; 163(5): 2555 - 2560. [Abstract] [Full Text] [PDF]

				S. Pascolo, N. Bervas, J. M. Ure, A. G. Smith, F. A. Lemonnier, and B. Perarnau HLA-A2.1-restricted Education and Cytolytic Activity of CD8+ T Lymphocytes from beta 2 Microglobulin (beta 2m) HLA-A2.1 Monochain Transgenic H-2Db beta 2m Double Knockout Mice J. Exp. Med., June 16, 1997; 185(12): 2043 - 2051. [Abstract] [Full Text] [PDF]