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 (beta 2i) 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/D-h and NP205-212/K-b in MECL-1(-/-) mice. The weak CTL response to GP276-286/D-b was not due to an impaired generation of this epitope but was attributed to a decreased precursor frequency of GP276-286D(b) -specific T cells. The expansion of TCR-V(beta)10(+) T cells, which contain GP276-286/D-b-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.