An altered T cell repertoire in MECL-1-deficient mice.
Immunoproteasome subunits low-molecular mass polypeptide (LMP)2 and LMP7 affect Ag presentation by MHC class I molecules. In the present study, we investigated the function of the third immunosubunit LMP10/multicatalytic endopeptidase complex-like (MECL)-1 (beta2i) in MECL-1 gene-targeted mice. The number of CD8+ splenocytes in MECL-1-/- mice was 20% lower than in wild-type mice. Infection with lymphocytic choriomeningitis virus (LCMV) elicited a markedly reduced cytotoxic T cell (CTL) response to the LCMV epitopes GP276-286/Db and NP205-212/Kb in MECL-1-/- mice. The weak CTL response to GP276-286/Db was not due to an impaired generation of this epitope but was attributed to a decreased precursor frequency of GP276-286/Db-specific T cells. The expansion of TCR-Vbeta10+ T cells, which contain GP276-286/Db-specific cells, was reduced in LCMV-infected MECL-1-/- mice. Taken together, our data reveal an in vivo function of MECL-1 in codetermining the T cell repertoire for an antiviral CTL response.
Basler
Michael
M
Division of Immunology, Department of Biology, University of Constance, Konstanz, Germany.
Moebius
Jacqueline
J
Elenich
Laura
L
Groettrup
Marcus
M
Monaco
John J
JJ
D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D001117:Arenaviridae Infections / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000821:virology; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D018390:Gene Targeting; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D008099:Liver / Q000201:enzymology / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D008231:Lymphopenia / Q000201:enzymology / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism; D061988:Proteasome Inhibitors; D016176:T-Lymphocyte Subsets / Q000201:enzymology* / Q000276:immunology* / Q000637:transplantation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000473:pathology
D016056:Immunodominant Epitopes; D061988:Proteasome Inhibitors; C071313:LMP-2 protein; D020169:Caspases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; C490920:Psmb10 protein, mouse