Nuclear myxovirus-resistance protein Mx is a minor histocompatibility antigen.
Minor histocompatibility antigens (MiHAgs) cause slow-to-rapid organ transplant rejection by immunocompetent hosts and mild-to-severe graft-versus-host reactions in immunosuppressed hosts. MiHAgs are allelic forms of major histocompatibility complex (MHC) class I-restricted self-antigens recognized by cytotoxic T cells and usually are defined immunogenetically. Although structurally not identified as yet, it is assumed that MiHAgs are internal cell antigens that are processed and then presented by MHC class I proteins similar to viral antigens. To define a MiHAg both molecularly and functionally, we took advantage of the allelic difference of the structurally characterized intracellular myxovirus-resistance protein (Mx) and investigated its antigenicity. Skin grafts from congenic Mx+ mice carrying the functional Mx1 gene were rejected by mice lacking a functional Mx1 gene (Mx- mice). In parallel, cytotoxic MHC class I-restricted effector T cells specific for Mx protein and the H-2Kk antigen (but not for several other allelic H-2 antigens) were strongly induced in Mx- mice immunized with spleen cells from interferon-treated Mx+ mice. These data show that allelic forms of cell internal proteins presented by MHC class I may act as MiHAgs.
Speiser
D E
DE
Institute of Pathology, University of Zürich, Switzerland.
Zürcher
T
T
Ramseier
H
H
Hengartner
H
H
Staeheli
P
P
Haller
O
O
Zinkernagel
R M
RM
D000483:Alleles; D000818:Animals; D000998:Antiviral Agents / Q000235:genetics*; D015153:Blotting, Western; D003433:Crosses, Genetic; D003602:Cytotoxicity, Immunologic; D005260:Female; D019204:GTP-Binding Proteins; D006084:Graft Rejection; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D015778:Minor Histocompatibility Antigens / Q000235:genetics*; D064547:Myxovirus Resistance Proteins; D009975:Orthomyxoviridae / Q000276:immunology; D011506:Proteins / Q000235:genetics* / Q000276:immunology; D016038:Skin Transplantation; D013045:Species Specificity; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000998:Antiviral Agents; D015778:Minor Histocompatibility Antigens; C579070:Mx1 protein, mouse; D064547:Myxovirus Resistance Proteins; D011506:Proteins; D019204:GTP-Binding Proteins