| First Author | Rajagopalan G | Year | 2003 |
| Journal | Tissue Antigens | Volume | 62 |
| Issue | 2 | Pages | 149-61 |
| PubMed ID | 12889995 | Mgi Jnum | J:137007 |
| Mgi Id | MGI:3797482 | Doi | 10.1034/j.1399-0039.2003.00088.x |
| Citation | Rajagopalan G, et al. (2003) Expression and function of HLA-DR3 and DQ8 in transgenic mice lacking functional H2-M. Tissue Antigens 62(2):149-61 |
| abstractText | H2-M or HLA-DM are non-classical class II molecules encoded by the MHC and play an important role during antigen presentation. They catalyze exchange of CLIP (Class II-associated invariant chain peptide) or other low-affinity peptides bound to class II molecules for peptides capable of more efficient binding. The phenotype of mice lacking H2-M is determined by the allotype of the MHC class II molecules expressed. In general, H2-M deficiency does not affect the surface expression of mature class II molecules. The class II molecules in such cases predominantly contain CLIP in their peptide-binding groove. In some mice strains, H2-M deficiency results in defective CD4+ T-cell development accompanied by defective responses to conventional antigens and superantigens. Even though the HLA class II molecules show similar dependency for HLA-DM for presenting antigens in vitro, their interaction in vivo is not known. By using transgenic approach we show here that DQ8 and DR3 are expressed at normal levels in H2-M-deficient mice and the CD4+ T-cell development is unaltered. However, the ability of DQ8 molecules to present peptide antigens is compromised in a H2-M-deficient state. Presentation of exogenous bacterial superantigens by both DQ8 and DR3 is unaffected in H2-M-deficient mice. Unexpectedly, Staphylococcal Enterotoxin B-induced systemic IFN-gamma production was significantly higher in H2-M-deficient DQ8/DR3 transgenic mice and these mice were susceptible to SEB-induced toxic shock at doses that are non-lethal to H2-M-sufficient counterparts. |
