Antiviral immune responses of mice lacking MHC class II or its associated invariant chain.
Induction of T-helper cells and T-B cell interaction have been considered to critically depend upon recognition of major histocompatibility complex (MHC) class II molecules by the T cell receptor. Mice lacking either MHC class II molecules (class II(0/0) mice) or its associated invariant chain (Ii0/0 mice) provide new opportunities to test this premise. Immune responses to some protein antigens have been studied in these mice; little is known about their ability to withstand viral infections. We therefore tested CD8+ effector T cells and CD4+ T-cell-dependent B cell function during different viral infections. The vesicular stomatitis virus (VSV)-specific primary cytotoxic T cell response which is largely T-helper-dependent was diminished in Ii(0/0) and absent in class II(0/0) mice. The usually less T-helper-dependent cytotoxic vaccinia or lymphocytic choriomeningitis virus (LCMV)-specific CD8+ T cell responses were reduced up to ninefold in class II(0/0) and up to threefold in Ii(0/0) mice. In class II(0/0) mice, the T-helper-independent neutralizing IgM response against the glycoprotein of VSV was within normal ranges but, in contrast to previous results on CD4(0/0) mice, the T-helper-dependent IgG response was absent. Ii(0/0) mice exhibited a normal neutralizing IgM response; in contrast to class II(0/0) mice, they mounted a significant, though reduced specific IgG response. Similar results were obtained for antibody responses against the nucleoprotein of VSV. Although the T-helper-cell response upon infection with VSV seemed diminished only a little in Ii(0/0) mice, presentation of VSV-G to a class II-restricted specific hybridoma was greater than 300-fold reduced in the absence of Ii. This suggests that local protein concentrations reached during viral infection in the host are high enough to override the Ii deficiency of antigen-presenting cells in vivo.
Institute of Experimental Immunology, Department of Pathology, University of Zurich, Switzerland.
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M
Battegay
M F
MF
Bachmann
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C
Burhkart
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S
Viville
C
C
Benoist
D
D
Mathis
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Hengartner
R M
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Zinkernagel
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis*; D000938:Antigen-Presenting Cells / Q000502:physiology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000502:physiology*; D002213:Capsid / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000502:physiology*; D008562:Membrane Glycoproteins; D051379:Mice; D008810:Mice, Inbred C57BL; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014758:Viral Core Proteins / Q000276:immunology; D014759:Viral Envelope Proteins / Q000276:immunology
D000914:Antibodies, Viral; D000944:Antigens, Differentiation, B-Lymphocyte; C028391:G protein, vesicular stomatitis virus; D000949:Histocompatibility Antigens Class II; D008562:Membrane Glycoproteins; D014758:Viral Core Proteins; D014759:Viral Envelope Proteins; C045084:invariant chain