Strong xenogeneic HLA response in transgenic mice after introducing an alpha 3 domain into HLA B27.
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.
German Cancer Research Center, Institute of Immunology and Genetics, Heidelberg.
U
U
Kalinke
B
B
Arnold
G J
GJ
Hämmerling
D000595:Amino Acid Sequence; D000818:Animals; D003433:Crosses, Genetic; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000032:analysis; D006183:H-2 Antigens / Q000235:genetics / Q000302:isolation & purification; D015796:HLA-B27 Antigen / Q000235:genetics*; D006649:Histocompatibility Antigens / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000939:Epitopes; D006183:H-2 Antigens; D015796:HLA-B27 Antigen; D006649:Histocompatibility Antigens