Strong xenogeneic HLA response in transgenic mice after introducing an alpha 3 domain into HLA B27

Nature. 1990 Dec 13;348(6302):642-4. doi: 10.1038/348642a0.


The pronounced response by mouse T cells to the major histocompatibility complex (MHC) class I antigens of the same species is characterized by a relatively large fraction of responding cells. Responses to MHC class I allelles of other species are, however, generally much weaker. T lymphocytes are positively selected on thymic MHC antigens, resulting in a T-cell repertoire with strong alloreactivity. This has been explained in terms of a mouse T-cell repertoire that is not efficiently selected for recognition of HLA molecules owing to the absence of HLA in mice. Here we show that mice transgenic for HLA mount a T-cell response against allogeneic HLA that is no better than in normal mice. We decided instead to test whether the mouse accessory molecule Lyt-2 on cytotoxic T lymphocytes could interact efficiently with the alpha 3 domain of HLA. To do this, we replaced the alpha 3 domain of HLA-B27 by a murine alpha 3 domain in a gene construct used to produce transgenic mice, and then used the spleen cells from these mice to stimulate normal mouse T cells. Under these conditions cytotoxic T lymphocytes were generated with the same frequency against xenogeneic HLA-B27 determinants as against allogeneic mouse class I antigens. These findings indicate that the normally weak xeno-MHC response is due to the inefficient interaction of the murine Lyt-2 accessory molecule with HLA class I, and not to limitations of the mouse T-cell repertoire.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Crosses, Genetic
  • Cytotoxicity, Immunologic
  • Epitopes / analysis
  • H-2 Antigens / genetics
  • H-2 Antigens / isolation & purification
  • HLA-B27 Antigen / genetics*
  • Histocompatibility Antigens / genetics*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mice, Transgenic
  • Molecular Sequence Data
  • T-Lymphocytes / immunology*
  • T-Lymphocytes, Cytotoxic / immunology


  • Epitopes
  • H-2 Antigens
  • HLA-B27 Antigen
  • Histocompatibility Antigens