Influence of H-2 class II antigens on the development of murine AIDS.
Inbred strains of mice differ markedly in their relative susceptibility to the development of lymphoproliferation and immunodeficiency, a syndrome termed mouse AIDS (MAIDS), after infection with the LP-BM5 mixture of murine leukemia viruses (MuLV). The etiologic virus in this mixture is replication defective (BM5def) and encodes only a variant gag protein. Genetic determinants of resistance and susceptibility to induction of MAIDS reside both within and outside the MHC. In strains with C57BL background genes, the MHC haplotypes associated with resistance to disease include d and a, whereas haplotypes b, s, and q are associated with sensitivity. Previous studies showed that MHC class I genes (H-2Dd, H-2Ld) mapping in the D end of H-2 and other genes mapping proximal to the D end determine resistance to MAIDS. This paper examines the nature of these non-D end MHC genes using assays of MHC recombinant and transgenic mice. We demonstrate that expression of E alpha d confers significant resistance to MAIDS, even in mice that do not express H-2Dd/H-2Ld. Unexpectedly, we found that E alpha polymorphisms can significantly influence resistance, with H-2b mice bearing E alpha d as a transgene having greater resistance to MAIDS than mice bearing an E alpha k transgene. E alpha d-mediated resistance to MAIDS was associated with decreased levels of the BM5def genome in splenic DNA, suggesting that E alpha genes exert their effect by enhancing antiviral activity.
Makino
M
M
Laboratory of Immunopathology, National Institute of Allergy and infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
Tang
Y
Y
Murphy
D B
DB
Fredrickson
T N
TN
Okada
Y
Y
Fujiwara
M
M
Chattopadhyay
S K
SK
Mizuochi
T
T
Komuro
K
K
Morse
H C
HC
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D006183:H-2 Antigens / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007113:Immunity, Innate; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic / Q000276:immunology; D016183:Murine Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000276:immunology*; D018089:Superantigens / Q000276:immunology
D000956:Antigens, Viral; D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D018089:Superantigens