Evidence of selective processing of immunodominant epitopes in virally infected cells

Recent advances in clarifying the molecular mechanisms involved in Ag proce ssing and presentation have relied heavily on the use of somatic cell mutan ts deficient in proteasome subunits, TAP transporter, and cell surface expr ession of MHC class I molecules, Of particular interest currently are those mutants that lack specific protease activity involved in the generation of antigenic peptides, It is theoretically possible that deficiencies of this nature could selectively prevent the cleavage of certain peptide bonds and thus generate only a subset of antigenic peptides, Gro29/K-b cell line is derived from the wild-type murine Ltk(-) cell line. This cell line is one e xample of a mutant that lacks specific protease activities. This deficiency manifests itself in an inability to generate a subset of immunodominant pe ptide epitopes derived from vesicular stomatitis virus and herpes simplex v irus. This in turn leads to a general inability to present these viral epit opes to cytotoxic T lymphocytes (CTL). These studies describe a unique Ag p rocessing deficiency and provide new insight into the role of proteasome-in dependent proteases in MHC class I-restricted peptide generation.