| First Author | Harada N | Year | 2017 |
| Journal | J Immunol | Volume | 198 |
| Issue | 1 | Pages | 516-527 |
| PubMed ID | 27881704 | Mgi Jnum | J:299379 |
| Mgi Id | MGI:6490883 | Doi | 10.4049/jimmunol.1502367 |
| Citation | Harada N, et al. (2017) Generation of a Novel HLA Class I Transgenic Mouse Model Carrying a Knock-in Mutation at the beta2-Microglobulin Locus. J Immunol 198(1):516-527 |
| abstractText | We generated a series of monochain HLA class I knock-in (KI) mouse strains, in which a chimeric HLA class I molecule (alpha1/alpha2 domain of HLA-A*0201, HLA-A*0301, HLA-A*2402, or HLA-A*3101 and alpha3 domain of H-2D(b)) was covalently linked with 15 aa to human beta2-microglobulin (beta2m) and introduced into the endogenous mouse beta2m locus. In homozygous KI mice, mouse beta2m gene disruption resulted in loss of the endogenous H-2 class I molecules and reduction in the peripheral CD8(+) T cell population that was partially restored by monochain HLA class I expression. A gene dosage-dependent expression of HLA, similar to that in human PBMCs, was detected in heterozygous and homozygous HLA KI mice. Upon vaccination with various virus epitopes, HLA-restricted, epitope-specific CTLs were induced in HLA KI mice, similar to the response in the commonly used HLA transgenic mice. Importantly, the CTL responses induced in heterozygous KI mice were similar to those in homozygous KI mice. These results suggest that coexpression of H-2 class I does not affect HLA-restricted CTL responses in HLA KI mice, which differs from the situation reported for monochain HLA Tg x beta2m(-/-) mice. Furthermore, we generated double KI mice harboring two different HLA (HLA-A*2402 and HLA-A*0301) KI alleles, which showed a CTL response against both HLA-A24 and HLA-A3 epitopes when immunized with a mixture of both peptides. These results indicated that this HLA class I KI mouse model provides powerful research tools not only for the study of HLA class I-restricted CTL responses, but also for preclinical vaccine evaluation. |
