MHC class I molecule-restricted presentation of viral antigen in beta 2-microglobulin-deficient mice.
Normally, Ag is presented to CD8+ T lymphocytes as a tripartite complex consisting of peptide epitope, MHC-encoded class I heavy (alpha) chain, and beta 2-microglobulin (beta 2-m) light chain. Although there is agreement about the function of both peptide and alpha-chain, the role of beta 2-m has remained uncertain. In particular, can Ag be presented without its participation? We have sought to obtain an answer by using mice in which the gene for beta 2-m had been disrupted by homologous recombination. As a consequence, no light chains are synthesized and, furthermore, few if any CD8+ T lymphocytes are formed. Elimination of lymphocytic choriomeningitis (LCM) virus from the tissues of acutely infected mice is mediated solely by CD8+ T lymphocytes; hence, in the beta 2-m-lacking mutants the infection cannot be terminated. Here it is shown that infusion of immune spleen cells from syngeneic beta 2-m+/+ mice and from mice compatible in K or D of the MHC resulted in virus clearance. Approximately five times more cells were required to achieve antiviral effects in beta 2-m-deficient than in wild-type mice but attempts to improve elimination by treatment of the former with IFN-gamma or beta 2-m have failed. Depleting the immune splenocytes of CD8+ T lymphocytes but not of CD4+ T lymphocytes abolished the antiviral potential. We conclude that LCM virus-infected murine cells can present viral Ag to CD8+ effector T lymphocytes together with class I MHC molecules K and D, despite the total absence of beta 2-m.
Lehmann-Grube
F
F
Heinrich Pette Institute for Experimental Virology and Immunology, University of Hamburg, Germany.
Dralle
H
H
Utermöhlen
O
O
Löhler
J
J
D000818:Animals; D017951:Antigen Presentation; D000956:Antigens, Viral / Q000276:immunology*; D016827:CD8 Antigens / Q000032:analysis; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000502:physiology*; D016219:Immunotherapy, Adoptive; D008099:Liver / Q000473:pathology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D008297:Male; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology; D001613:beta 2-Microglobulin / Q000172:deficiency*
D000956:Antigens, Viral; D016827:CD8 Antigens; D015395:Histocompatibility Antigens Class I; D001613:beta 2-Microglobulin