Proteasome subunits encoded in the MHC are not generally required for the processing of peptides bound by MHC class I molecules
- 12 November 1992
- journal article
- Published by Springer Science and Business Media LLC in Nature
- Vol. 360 (6400), 171-174
- https://doi.org/10.1038/360171a0
Abstract
Antigen processing provides major histocompatibility complex (MHC) class I molecules with short peptides, which they selectively bind and present to cytotoxic T lymphocytes. The proteolytic system generating these peptides in the cytosol is unidentified, but their delivery into the endoplasmic reticulum is mediated by the TAP1-TAP2 transporter encoded in the MHC class II region. Closely linked to TAP1 and TAP2 are genes for the LMP2 and LMP7 proteins, which resemble components of proteasomes, proteolytic complexes known to degrade cytosolic proteins. This association has led to the common assumption that proteasomes function in this immunological pathway (discussed in ref. 15). We now show that the expression of stably assembled class I molecules and apparently normal peptide processing can be completely restored in the absence of LMP2 and LMP7 in the human lymphoblastoid cell line mutant 721.174 (refs 16, 17). The identity of LMP7 is directly confirmed by reconstitution of a proteasomal subunit after gene transfer. These results therefore dispute the hypothetical involvement of proteasomes in antigen processing, although a more subtle effect of LMP2 and LMP7 cannot be ruled out.Keywords
This publication has 32 references indexed in Scilit:
- A molecular model of MHC class-I-restricted antigen processingImmunology Today, 1992
- HLA-A2 molecules in an antigen-processing mutant cell contain signal sequence-derived peptidesNature, 1992
- Identification of self peptides bound to purified HLA-B27Nature, 1991
- Efficient cDNA expression vectors for stable and transient expression of HLA-DR in transfected fibroblast and lymphoid cellsHuman Immunology, 1991
- Peptide-induced conformational change of the class I heavy chainNature, 1991
- Restored expression of major histocompatibility class I molecules by gene transfer of a putative peptide transporterNature, 1991
- Allele-specific motifs revealed by sequencing of self-peptides eluted from MHC moleculesNature, 1991
- A gene in the human major histocompatibility complex class II region controlling the class I antigen presentation pathwayNature, 1990
- The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptidesCell, 1986
- Description of a monoclonal antibody defining an HLA allotypic determinant that includes specificities within the B5 cross-reacting groupHuman Immunology, 1982