Endogenous pathway of antigen presentation

We and our partners use cookies to Store and/or access information on a device. We and our partners use data for Personalised ads and content, ad and content measurement, audience insights and product development. An example of data being processed may be a unique identifier stored in a cookie. Some of our partners may process your data as a part of their legitimate business interest without asking for consent. To view the purposes they believe they have legitimate interest for, or to object to this data processing use the vendor list link below. The consent submitted will only be used for data processing originating from this website. If you would like to change your settings or withdraw consent at any time, the link to do so is in our privacy policy accessible from our home page.. Antigen Processing and Presentation • Foreign protein antigen recognition by a T cell needs the presentation of peptides produced from the antigen within the cleft of an MHC molecule on the cell membrane. • The production of these peptide-MHC complexes requires the degradation of a protein antigen into peptides, a • The degraded peptides then bind to MHC molecules within the interior of the cell, and the peptide-MHC complexes are transported to the cell membrane, where they are displayed (antigen presentation). • Class I and class II MHC molecules bind to peptides processed in distinct intracellular compartments. • Class I MHC molecules bind cytoplasmically processed peptides generated from end...

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Immune checkpoint blockade, which blocks inhibitory signals of T cell activation, has shown tremendous success in treating cancer, although success still remains limited to a fraction of patients. To date, clinically effective CD8 + T cell responses appear to target predominantly antigens derived from tumour-specific mutations that accumulate in cancer, also called neoantigens. Tumour antigens are displayed on the surface of cells by class I human leukocyte antigens (HLA-I). To elicit an effective antitumour response, antigen presentation has to be successful at two distinct events: first, cancer antigens have to be taken up by dendritic cells (DCs) and cross-presented for CD8 + T cell priming. Second, the antigens have to be directly presented by the tumour for recognition by primed CD8 + T cells and killing. Tumours exploit multiple escape mechanisms to evade immune recognition at both of these steps. Here, we review the tumour-derived factors modulating DC function, and we summarize evidence of immune evasion by means of quantitative modulation or qualitative alteration of the antigen repertoire presented on tumours. These mechanisms include ...

In order to be capable of engaging the key elements of adaptive immunity (specificity, memory, diversity, self/nonself discrimination), antigens have to be processed and presented to immune cells. Antigen presentation is mediated by MHC class I molecules, and the class II molecules found on the surface of antigen-presenting cells (APCs) and certain other cells. MHC class I and class II molecules are similar in function: they deliver short peptides to the cell surface allowing these peptides to be recognised by CD8+ (cytotoxic) and CD4+ (helper) T cells, respectively. The difference is that the peptides originate from different sources – endogenous, or intracellular, for MHC class I; and exogenous, or extracellular for MHC class II. There is also so called cross-presentation in which exogenous antigens can be presented by MHC class I molecules. Endogenous antigens can also be presented by MHC class II when they are degraded through autophagy. Figure 1. The MHC class I antigen-presentation pathway. MHC class I presentation MHC class I molecules are expressed by all nucleated cells. MHC class I molecules are assembled in the endoplasmic reticulum (ER) and consist of two types of chain – a polymorphic heavy chain and a chain called β2-microglobulin. The heavy chain is stabilised by the chaperone calnexin, prior to association with the β2-microglobulin. Without peptides, these molecules are stabilised by chaperone proteins: calreticulin, Erp57, protein disulfide isomerase (PDI)...

MODELS for antigen presentation have divided the world of antigens into two categories, endogenous and exogenous 1–3, presented to T cells by class I and class II major histocompatibility complex (MHC) encoded molecules, respectively. Exogenous antigens are thought to be taken up into peripheral endosomal compartments where they are processed for binding to class II MHC molecules. Endogenous antigens are either synthesized 4–6or efficiently delivered to the cytoplasm 7,8before being partially degraded in an as yet undefined way, and complexed with class I MHC molecules. A useful phenotypic distinction between the two pathways has been the sensitivity to weak bases, such as chloroquine, which is a property only of the exogenous pathway 1. The fungal antibiotic brefeldin A (BFA), which blocks protein transport from the endoplasmic reticulum to the Golgi network 9–11, also blocks class I-restricted antigen-presentation, providing us with the corresponding marker of the endogenous pathway 12,13. Experiments with influenza virus antigens 1,14 have supported the view that class II MHC molecules can present exogenous but not endogenous antigen 1–3, whereas the observation that class II MHC molecules present measles virus non-membrane antigens by a chloroquine-insensitive pathway 15suggests that this is not always the case. We show here that influenza A matrix protein can be effectively presented to class II-restricted T cells by two pathways: one of which is chloroquine-sensitive...