Analysis of the HLA-Cw3-specific cytotoxic T lymphocyte response of HLA-B7 X human beta 2m double transgenic mice.
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.
Barra
C
C
Centre d'Immunologie INSERM-CNRS de Marseille-Luminy, France.
Pérarnau
B
B
Gerlinger
P
P
Lemeur
M
M
Gillet
A
A
Gibier
P
P
Lemonnier
F A
FA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000950:Antigens, Ly / Q000276:immunology; D001667:Binding, Competitive; D002469:Cell Separation; D002999:Clone Cells / Q000032:analysis; D006224:Cricetinae; D003601:Cytotoxicity Tests, Immunologic; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D015329:Gene Rearrangement, T-Lymphocyte; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology; D015793:HLA-B7 Antigen / Q000235:genetics / Q000276:immunology*; D015236:HLA-C Antigens / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008214:Lymphocytes / Q000032:analysis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic / Q000235:genetics / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000032:analysis; D001613:beta 2-Microglobulin / Q000235:genetics / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000950:Antigens, Ly; D000939:Epitopes; D006183:H-2 Antigens; D015793:HLA-B7 Antigen; D015236:HLA-C Antigens; C038653:HLA-C*03 antigen; D011948:Receptors, Antigen, T-Cell; D001613:beta 2-Microglobulin