| First Author | Rohrlich PS | Year | 2003 |
| Journal | Int Immunol | Volume | 15 |
| Issue | 6 | Pages | 765-72 |
| PubMed ID | 12750360 | Mgi Jnum | J:83720 |
| Mgi Id | MGI:2663356 | Doi | 10.1093/intimm/dxg073 |
| Citation | Rohrlich PS, et al. (2003) HLA-B*0702 transgenic, H-2KbDb double-knockout mice: phenotypical and functional characterization in response to influenza virus. Int Immunol 15(6):765-72 |
| abstractText | HLA-B*0702 transgenic mice (expressing a chimeric heavy chain with a murine alpha 3 domain: HLA-B7(m alpha 3)) in which the H-2K(b) and H-2D(b) class I-a (Cl I-a(-/-)) genes have been inactivated were compared with H-2K(b)D(b) Cl I-a(+/+) positive controls. Expression of the HLA-B7(m alpha 3) molecules resulted in a 3- to 4-fold increase in peripheral CD8(+) T lymphocyte numbers compared to H-2 Cl I-a(-/-) knockout mice. These cells show a diversified TCR repertoire. Following influenza infection, a significant improvement in HLA-B0702-restricted cytotoxic T lymphocyte (CTL) responses was observed in HLA-B7(m alpha 3), H-2 Cl I-a(-/-) compared to HLA-B7(m alpha 3), H-2 Cl I-a(+/+) mice. The CTL response of infected HLA-B7(m alpha 3), H-2 Cl I-a(-/-) mice was directed against the nucleoprotein (NP) 418-426 epitope in which mutations have accumulated. Whereas all NP 418-426 variant peptides induced a CTL response, cross-reactivity to the variants was affected. These NP mutations could have been selected over time in humans for the virus to escape HLA-B0702-restricted CTL responses since a similar response was seen in humans with, as in mice, altered cross-recognition of the NP 418-426 variants. These animals may prove a suitable model to study HLA-B0702-restricted CTL responses. |
