The Biochemistry and Cell Biology of Antigen Processing and Presentation

Germain, Ronald N.; Margulies, David H.

doi:10.1146/annurev.iy.11.040193.002155

Cited by 968 publications

(359 citation statements)

References 174 publications

Supporting

Mentioning

343

Contrasting

Unclassified

Order By: Relevance

“…In contrast, association with the invariant chain prevents MHC class II molecules from binding peptides in the endoplasmic reticulum and directs these molecules to the late endocytic compartment for binding endocytosed exogenous protein-derived antigens. Thus, separate pathways for peptide presentation mediated by these two classes of antigenpresenting molecules result in efficient sampling in distinct intracellular compartments (29). For presentation of lipid antigens, CD1a samples early recycling endosomes whereas the cytoplasmic signal directs CD1b to penetrate deeply into the endocytic system to sample the late endocytic compartment.…”

Section: Discussionmentioning

confidence: 99%

CD1c molecules broadly survey the endocytic system

Sugita

Wel

Rogers

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

109

View full text Add to dashboard Cite

The ability of antigen-presenting cells to sample distinct intracellular compartments is crucial for microbe detection. Major histocompatibility complex class I and class II molecules sample the cytosol or the late endocytic compartment, allowing detection of microbial peptide antigens that arise in distinct intracellular compartments. In contrast, CD1a and CD1b molecules mediate the presentation of lipid and glycolipid antigens and differentially sample early recycling endosomes or late endocytic compartments, respectively, that contain distinct sets of lipid antigens. Here, we show that, unlike the other CD1 isoforms or major histocompatibility complex molecules that each sample restricted only intracellular compartments, CD1c is remarkable in that it distributes broadly throughout the endocytic system and is expressed in both recycling endosomes and late endocytic compartments. Further, in contrast to CD1b, which requires an acidic environment to function, antigen presentation by CD1c was able to overcome dependence on vesicular acidification. Because CD1c is expressed on essential antigen-presenting cells, such as epidermal Langerhans cells (in the absence of CD1b), or on B cells (without CD1a or -b), we suggest that CD1c molecules allow a comprehensive survey for lipid antigens throughout the endocytic system even in the absence of other CD1 isoforms.

show abstract

Section: Discussionmentioning

confidence: 99%

CD1c molecules broadly survey the endocytic system

Sugita

Wel

Rogers

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

109

View full text Add to dashboard Cite

show abstract

“…Subsequently, class I-peptide complexes are transported to the cell surface, where they can be recognized by the appropriate CD8 ÷ T lymphocytes (for review see [1,2]). …”

Section: Introductionmentioning

confidence: 99%

Functional expression and purification of the ABC transporter complex associated with antigen processing (TAP) in insect cells

et al. 1994

View full text Add to dashboard Cite

Using the baculovirus expression system the gene products of human tapl and tap2 were over-expressed as wild-type as well as oligohistidine fusion proteins in Spodopterafrugiperda (Sf9) insect cells, Both gene products were co-expressed within the same cells and were found enriched in microsomal membranes. Immunoprecipitation and immobilized metal affinity chromatography revealed complex formation between TAP1 and TAP2. The expressed TAP complex was shown to be functional by peptide translocation into microsomes of Sf9 cells. Peptide transport strictly requires TAP1 and TAP2 as well as ATE For the first time the functional expression ofthe human TAP complex in insect cells has been demonstrated, indicating that additional cofactors of a highly developed immune system are not essential for peptide transport across microsomal membranes.

show abstract

“…Major histocompatibility complex (MHC) class I molecules are ubiquitously expressed heterodimers of a class I heavy chain and 132-microglobulin (f32m), which display peptides derived from proteins degraded in the cytosol on the cell surface and thus facilitate the recognition of intracellular antigens by circulating cytotoxic CD8+ T cells with ac3 T-cell receptors (1,2). Class I related molecules have variously altered functions, including the presentation of lipid and lipoglycan compounds to CD4-8-T cells by human CDlb encoded outside the MHC (3,4).…”

mentioning

confidence: 99%

Cell stress-regulated human major histocompatibility complex class I gene expressed in gastrointestinal epithelium.

Groh

Bahram

Bauer

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

940

833

View full text Add to dashboard Cite

Conventional major histocompatibility complex (MHC) class I genes encode molecules that present intracellular peptide antigens to T cells. They are ubiquitously expressed and regulated by interferon y. Two highly divergent human MHC class I genes, MICA and MICB, are regulated by promoter heat shock elements similar to those ofHSP70 genes. MICA encodes a cell surface glycoprotein, which is not associated with f82-microglobulin, is conformationally stable independent of conventional class I peptide ligands, and almost exclusively expressed in gastrointestinal epithelium. Thus, this MHC class I molecule may function as an indicator of cell stress and may be recognized by a subset of gut mucosal T cells in an unusual interaction. tant cell lines, as well as in immunohistology stainings. The results show that MICA is a.highly glycosylated membraneanchored cell surface protein that is not associated with ,32mand is conformationally stable in the absence of conventional MHC class I peptide ligands. In accord with previous concepts, the almost exclusive expression of MICA in gastrointestinal epithelium combined with the intriguing transcriptional regulation of the MICA gene by a promoter heat shock element implies that this MHC class I molecule may function as a ligand for a subset of T cells in the intestinal intraepithelial lymphocyte compartment. This putative interaction is probably unrelated to conventional MHC class I antigen presentation and may serve a specialized T-cell immune surveillance function.Major histocompatibility complex (MHC) class I molecules are ubiquitously expressed heterodimers of a class I heavy chain and 132-microglobulin (f32m), which display peptides derived from proteins degraded in the cytosol on the cell surface and thus facilitate the recognition of intracellular antigens by circulating cytotoxic CD8+ T cells with ac3 T-cell receptors (1, 2). Class I related molecules have variously altered functions, including the presentation of lipid and lipoglycan compounds to CD4-8-T cells by human CDlb encoded outside the MHC (3, 4). Moreover, so-called nonclassical MHC class I molecules in the mouse selectively present bacterial peptides (5, 6), are recognized by T cells with y6 T-cell receptors in the absence of detectable bound peptides (7-10), or are mainly expressed in intestinal epithelium where they may interact with a subset of the resident T cells (11,12). Although the precise functions of some of these molecules remain to be defined, they are conceptually appreciated as potential components of a firstline immune defense (13,14). However, functionally corresponding genes and molecules have not been found in other mammals and humans. Conversely, two highly divergent human MHC class I genes closely linked to HLA-B, MICA, and MICB are conserved in most if not all mammals but seem to be missing in the mouse (15,16). These genes are transcribed in epithelial cell lines but not in B cells, T cells, and monocytes and are not induced by interferon y. Their translation products share an exc...

show abstract

The Biochemistry and Cell Biology of Antigen Processing and Presentation

Cited by 968 publications

References 174 publications

CD1c molecules broadly survey the endocytic system

CD1c molecules broadly survey the endocytic system

Functional expression and purification of the ABC transporter complex associated with antigen processing (TAP) in insect cells

Cell stress-regulated human major histocompatibility complex class I gene expressed in gastrointestinal epithelium.

Contact Info

Product

Resources

About