Expression and function of HLA-DR3 and DQ8 in transgenic mice lacking functional H2-M.
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.
Rajagopalan
G
G
Department of Immunology, Mayo Clinic, Rochester, MN, USA.
Smart
M K
MK
Cheng
S
S
Krco
C J
CJ
Johnson
K L
KL
David
C S
CS
D000818:Animals; D000941:Antigens / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D004768:Enterotoxins / Q000276:immunology; D006683:HLA-DQ Antigens / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D015803:HLA-DR3 Antigen / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000276:immunology; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D010455:Peptides / Q000235:genetics / Q000276:immunology / Q000502:physiology; D012772:Shock, Septic / Q000276:immunology; D018089:Superantigens / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology
D000941:Antigens; D004768:Enterotoxins; C416189:H2-M antigens; D006683:HLA-DQ Antigens; C109756:HLA-DQ8 antigen; D015803:HLA-DR3 Antigen; D000949:Histocompatibility Antigens Class II; D010455:Peptides; D018089:Superantigens; C031818:enterotoxin B, staphylococcal