Antigen bias in T cell cross-priming.

Activated CD8+ T cells detect virally infected cells and tumor cells by recognition of major histocompatibility complex class I-bound peptides derived from degraded, endogenously produced proteins. In contrast, CD8+ T cell activation often occurs through interaction with specialized antigen-presenting cells displaying peptides acquired from an exogenous cellular source, a process termed cross-priming. Here, we observed a marked inefficiency in exogenous presentation of epitopes derived from signal sequences in mouse models.

TCR reconstitution in Jurkat reporter cells facilitates the identification of novel tumor antigens by cDNA expression cloning.

The identification of novel tumor antigens is of extreme importance for effective immunotherapy against cancer. A major obstacle in this field is the limited life span of tumor-specific cytotoxic T lymphocytes (CTLs) in vitro. Therefore we searched for a method to isolate the tumor specificity of these CTLs, i.

MHC class I molecules can direct proteolytic cleavage of antigenic precursors in the endoplasmic reticulum.

The large set of peptides presented by MHC (major histocompatibility complex) class I molecules are generated by proteolysis of diverse precursors in the cytoplasm and possibly in the endoplasmic reticulum (ER). To define the potential peptide trimming events in the ER, we analyzed proteolytic products generated in isolated microsomes. The residues flanking the N terminus of the final antigenic peptide were rapidly removed within the microsomes but only in the presence of appropriate MHC molecules.

Differences that matter: major cytotoxic T cell-stimulating minor histocompatibility antigens.

Despite thousands of genetic polymorphisms among MHC matched mouse strains, a few unknown histocompatibility antigens are targeted by the cytotoxic T cells specific for tissue grafts. We isolated the cDNA of a novel BALB.B antigen gene that defines the polymorphic H28 locus on chromosome 3 and yields the naturally processed ILENFPRL (IFL8) peptide for presentation by Kb MHC to C57BI/6 CTL.

Discrete proteolytic intermediates in the MHC class I antigen processing pathway and MHC I-dependent peptide trimming in the ER.

The antigen processing pathway generates the peptides displayed by MHC I molecules on the cell surface. Whether these peptides are generated in the cytosol or from longer intermediates transported into the ER is unclear, because peptides other than those bound to MHC I have been difficult to find. Using a novel assay, we show that N-terminally extended antigenic analogs were associated with high-molecular weight material in the cytosol and were transported by TAP.