Antigen Processing and Presentation by the Class I Major Histocompatibility Complex

York, Ian A.; Rock, Kenneth L.

doi:10.1146/annurev.immunol.14.1.369

Cited by 559 publications

(329 citation statements)

References 187 publications

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“…In contrast, a CMM study revealed strong tyrosinase and MHCI mRNA expression in all tumours evaluated irrespective of the degree of tumour pigmentation (Phillips et al, 2012). It should be noted, however, that although these mRNA data are supportive of active gene transcription, one could not conclude that the encoded proteins are properly translated, proteolytically processed and correctly oriented within the cell, which is of key importance to effective antigen presentation (York and Rock, 1996). Another peculiarity of some human melanoma cells is their ability to constitutively express MHCII and this is often associated with a poor prognosis (D'Alessandro et al, 1987;Martins et al, 2009;Ostmeier et al, 2001).…”

Section: Possible Immunological Reasons For Lack Of Efficacymentioning

confidence: 84%

Cancer immunology and canine malignant melanoma: A comparative review

Atherton

Morris

McDermott

et al. 2016

Veterinary Immunology and Immunopathology

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Canine melanoma as a model of human melanomaFor at least two decades, veterinary oncologists have advocated using spontaneously occurring tumours in companion animals as models for human cancer (Knapp and Waters, 1997;MacEwen, 1990). Several recent reviews have readdressed this approach identifying osteosarcoma, mammary tumours, head and neck cancers, bladder carcinomas, non-Hodgkin lymphoma, prostatic carcinoma, lung cancer and pertinently oral canine malignant melanoma (CMM) as good models for human neoplasms (Hansen and Khanna, 2004;Khanna and Hunter, 2005;Paoloni and Khanna, 2008). The major benefits of dogs as tumour models include the ability to study genetically outbred and immunologically intact animals in which cancers develop spontaneously and thus, more likely reflect the process of tumourigenesis compared to experimentally-induced neoplasms. As pets and owners share the same environment, they may be exposed to the same carcinogens, which, in part, drive tumour development. Regarding disease modelling, animal tumours often have similar clinical presentation, tumour biology and histopathological appearance to their human counterparts and usually progress more rapidly, thereby shortening data maturation times. In addition, few "standard of care" therapies exist for dogs meaning that within reason, trial therapeutics can be instigated at any point. Given these benefits, companion animal tumour models more accurately reflect the features of human cancers compared to rodent models with CMM being a desirable example of one such neoplasm. Conversely, the opportunity to translate the potential value of state of the art human therapeutics to the veterinary clinic also exists. Oral canine malignant melanoma (CMM) is a spontaneously occurring aggressive tumour with relatively few medical treatment options, which provides a suitable model for the disease in humans. Historically, multiple immunotherapeutic strategies aimed at provoking both innate and adaptive anti-tumour immune responses have been published with varying levels of activity against CMM. Recently, a plasmid DNA vaccine expressing human tyrosinase has been licensed for the adjunct treatment of oral CMM. This article reviews the immunological similarities between CMM and the human counterpart; mechanisms by which tumours evade the immune system; reasons why melanoma is an attractive target for immunotherapy; the premise of whole cell, dendritic cell (DC), viral and DNA vaccination strategies alongside preliminary clinical results in dogs. Current "gold standard" treatments for advanced human malignant melanoma are evolving quickly with remarkable results being achieved following the introduction of immune checkpoint blockade and adoptively transferred cell therapies. The rapidly expanding field of cancer immunology and immunotherapeutics means that rational targeting of this disease in both species should enhance treatment outcomes in veterinary and human clinics.

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Section: Possible Immunological Reasons For Lack Of Efficacymentioning

confidence: 84%

Cancer immunology and canine malignant melanoma: A comparative review

Atherton

Morris

McDermott

et al. 2016

Veterinary Immunology and Immunopathology

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“…Most of these peptides are generated by protein breakdown in the cytosol and are transported by the transporter associated with antigen presentation transporter into the endoplasmic reticulum (1). Here the peptide, a MHC class I heavy chain, and a ␤ 2 -microglobulin molecule associate, and the complex is then transported through the Golgi apparatus to the plasma membrane (1).…”

mentioning

confidence: 99%

Lactacystin and clasto-Lactacystin β-Lactone Modify Multiple Proteasome β-Subunits and Inhibit Intracellular Protein Degradation and Major Histocompatibility Complex Class I Antigen Presentation

Craiu

Gaczyńska

Akopian

et al. 1997

Journal of Biological Chemistry

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366

266

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The antibiotic lactacystin was reported to covalently modify ␤-subunit X of the mammalian 20 S proteasome and inhibit several of its peptidase activities. However, we demonstrate that [ 3 H]lactacystin treatment modifies all the proteasome's catalytic ␤-subunits. Lactacystin and its more potent derivative ␤-lactone irreversibly inhibit protein breakdown and the chymotryptic, tryptic, and peptidylglutamyl activities of purified 20 S and 26 S particles, although at different rates. Exposure to these agents for 1 to 2 h reduced the degradation of short-and long-lived proteins in four different mammalian cell lines. Unlike peptide aldehyde inhibitors, lactacystin and the ␤-lactone do not inhibit lysosomal degradation of an endocytosed protein. These agents block class I antigen presentation of a model protein, ovalbumin (synthesized endogenously or loaded exogenously), but do not affect presentation of the peptide epitope SIINFEKL, which does not require proteolysis for presentation. Generation of most peptides required for formation of stable class I heterodimers is also inhibited. Because these agents inhibited protein breakdown and antigen presentation similarly in interferon-␥-treated cells (where proteasomes contain LMP2 and LMP7 subunits in place of X and Y), all ␤-subunits must be affected similarly. These findings confirm our prior conclusions that proteasomes catalyze the bulk of protein breakdown in mammalian cells and generate the majority of class I-bound epitopes for immune recognition.

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“…The sequence of the peptide is clearly important in cytotoxic T cell recognition of the MHC class I͞peptide complex through the T cell receptor (3). Natural killer (NK) cells also bear receptors for MHC class I molecules (4-7).…”

mentioning

confidence: 99%

Peptides isolated from HLA-Cw*0304 confer different degrees of protection from natural killer cell-mediated lysis

Zappacosta

Borrego

Brööks

et al. 1997

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

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HLA class I molecules bind peptides derived from proteins degraded in the cytoplasm and display them for surveillance by the immune system. The recognition of HLA class I molecules by natural killer (NK) cells generally inhibits the lytic process. To investigate the role of peptides in the interaction between HLA class I molecules and NK receptors, we first had to identify representative endogenous peptides. Individual peptides bound to HLA-Cw*0304 were isolated and sequenced by tandem mass spectrometry. These peptides ranged in length from 8 to 11 residues and shared an alanine at position 2 and a C-terminal leucine. The murine transporters associated with antigen processing (TAP)-deficient cell line RMA-S was transfected with HLA-Cw*0304 to test whether HLA molecules loaded with a single peptide could deliver the inhibitory signal to NK cells expressing p58.2, which is a killer cell inhibitory receptor known to interact with HLA molecules bearing the HLA-Cw3 public epitope. We found that, in the absence of exogenous peptides, the HLACw*0304 transfectants were killed at levels comparable to untransfected RMA-S cells whereas protection from lysis required both HLA-Cw*0304 heavy chain expression and an exogenously added HLA-Cw*0304-binding peptide. Importantly, not only were HLA-Cw*0304-binding peptides required for protection, but the ability of individual peptides to provide protection differed widely. These studies indicate that the ability to distinguish between subsets of peptides may be a general feature of HLA class I recognition by NK cells.

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Antigen Processing and Presentation by the Class I Major Histocompatibility Complex

Cited by 559 publications

References 187 publications

Cancer immunology and canine malignant melanoma: A comparative review

Cancer immunology and canine malignant melanoma: A comparative review

Lactacystin and clasto-Lactacystin β-Lactone Modify Multiple Proteasome β-Subunits and Inhibit Intracellular Protein Degradation and Major Histocompatibility Complex Class I Antigen Presentation

Peptides isolated from HLA-Cw*0304 confer different degrees of protection from natural killer cell-mediated lysis

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