The antigen receptors of CD8+ cytotoxic T lymphocytes (CTL) recognise short peptide epitopes, usually 8-10 amino acids long, in conjunction with major histocompatibility complex (MHC) class I molecules. The mechanisms of peptide transport from the cytosol to the endoplasmic reticulum and subsequent assembly with MHC class I molecules are relatively well understood, but much less is known about the generation of these peptides.
Proteasomes are multi-subunit proteinases involved in the breakdown of both misfolded and regulatory proteins. They are believed to generate peptides which associate with MHC class I molecules. In eukaryotes the 20S proteasome core consists of four seven-membered rings composed of 14 different subunits belonging to either the alpha-type or beta-type subfamilies. The alpha type subunits form the outer rings; the beta the inner. The three catalytic beta type subunits have mutually exclusive alternatives, producing heterogeneity in the proteasome population. Two of the subunits with alternative forms, designated LMP7 [embl: L11045] and LMP2 [embl: Z14977], are encoded within the MHC [ Ehring B, 1996]. Experimental evidence supports the idea that they alter proteasome action, producing peptides capable of binding to class I molecules.
Craiu A, 1997
Two distinct proteolytic processes in the generation of a major histocompatibility complex class I-presented peptide.
Proc Natl Acad Sci U S A 94(20), 10850-10855 (1997)
Ehring B, 1996
Effects of major-histocompatibility-complex-encoded subunits on the peptidase and proteolytic activities of human 20S proteasomes. Cleavage of proteins and antigenic peptides.
Eur J Biochem 235(1-2), 404-415 (1996)
Baumeister W, 1997
Curr Opin Struct Biol 7(2), 273-278 (1997)