HLA-DQ? chain can present mouse endogenous provirus MTV-9 product and clonally delete Tcr V?5+ and V?11+ T cells in transgenic mice

Abstract

The elusive Mls gene(s) are mouse mammary tumor virus genes. The endogenous cotolerogen involved in the clonal deletion of Tcr V beta 5.1, 5.2, and 11 in H-2E+ mouse strains has been narrowed down to MTV-9. We demonstrate that similar to H-2E alpha molecules, human DQw6 beta chain mediated clonal deletion of Tcr V beta 5.1, 5.2, and 11 also requires the MTV-9 gene product. This shows that human class II molecules can present mouse retroviral antigen. Further, backcross analysis involving [B10.M(DQb) x DBA/1] suggest a second cotolerogen in the B10.M background in the clonal deletion of V beta 5-bearing T cells.

HLA transgenic mice as humanized mouse models of disease and immunity.

“…The hybrid molecule was able to present MTV superantigen (4). A DQ6 ␤ transgene in H2 f (H2-E negative) mice resulted in the expression of DQ6 ␤ A ␣ molecule capable of deleting T cell receptor V ␤ 11 and V ␤ 5 bearing lymphocytes (5,6). These studies showed that the human class II chain can pair with mouse class II chains and effectively interact with mouse CD4.…”

Negative and positive selection by HLA-DR3(DRw17) molecules in transgenic mice

“…Respective studies are relevant for attempts to establish transgenic models for HLA-linked autoimmune diseases. In previous reports selection was mainly anlayzed in transgenic mice expressing only a single HLA class II a or ~ chain which, however, formed heterodimers with the mouse class II chains, so that the observed selection was caused by the heterodimers (Elliott et al 1993, Lawrance et al 1989Zhou et al 1991Zhou et al , 1992. In DQw6 oq3 double transgenic no selection of v[~ subpopulations was observed (Nishimura et al 1990).…”