Abnormal anti-viral immune response in mice is corrected in HLA-B27.2-transgenic mice.
In contrast to the strong Sendai virus-specific cytotoxic T-lymphocyte (CTL) responses in C57BL/6 mice. H-2Kb mutant bm1 mice are nonresponders to Sendai virus. By appropriate crossings between HLA-B27 double-transgenic mice and Kb mutant bm1 mice, and after subsequent selection, H-2bm1 homozygous mice were produced expressing the human HLA-B27.2 and beta 2-microglobulin genes. Here we show that the introduction of a human HLA class I gene into the genome of the H-2bm1 Sendai virus-nonresponder mutant mice resulted in good responsiveness to Sendai virus, and in normal levels of Sendai virus-specific CTL precursors. The CTL response in the HLA-B27.2 double-transgenic H-2bm1 mice against Sendai virus was restricted by the HLA-B27.2 molecule. These results show the direct involvement of HLA class I molecules in regulation of the anti-viral CTL repertoire and represent for the first time a correction of abnormal anti-viral immunity in mice by incorporation of a human MHC class I (HLA-B27.2) gene.
Central Laboratory of The Netherlands Red cross Blood Transfusion Service, Amsterdam.
F
F
Kievits
W
W
Lokhorst
P
P
Ivanyi
D000818:Animals; D000939:Epitopes / Q000276:immunology; D006183:H-2 Antigens / Q000235:genetics*; D015796:HLA-B27 Antigen / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D010222:Parainfluenza Virus 1, Human / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000939:Epitopes; D006183:H-2 Antigens; D015796:HLA-B27 Antigen