Antigen processing and presentation: How can a foreign antigen be recognized in a sea of self proteins?

Singer, Debra F.; Linderman, Jennifer J.

doi:10.1016/s0022-5193(05)80387-x

Cited by 4 publications

(2 citation statements)

References 38 publications

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“…The relationship between these parameters and the level of antigen presentation could then be studied without concerns of inhibitor toxicity. Later versions of this model included self‐peptides and TCR and expanded the range of questions that could be asked: at what density are exogenous peptides presented relative to self‐peptides (133), and can higher pMHC affinity offset lower pMHC–TCR affinity to engage the same number of TCRs (41)?…”

Section: Modelsmentioning

confidence: 99%

Toward a multiscale model of antigen presentation in immunity

Kirschner

Chang

Riggs

et al. 2007

Immunological Reviews

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A functioning immune system and the process of antigen presentation in particular encompass events that occur at multiple length and time scales. Despite a wealth of information in the biological literature regarding each of these scales, no single representation synthesizing this information into a model of the overall immune response as it depends on antigen presentation is available. In this article, we outline an approach for integrating information over relevant biological and temporal scales to generate such a representation for major histocompatibility complex class II-mediated antigen presentation. In addition, we begin to address how such models can be used to answer questions about mechanisms of infection and new strategies for treatment and vaccines.

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Section: Modelsmentioning

confidence: 99%

Toward a multiscale model of antigen presentation in immunity

Kirschner

Chang

Riggs

et al. 2007

Immunological Reviews

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“…Details of the APC model are described elsewhere (1,8,59,60). Briefly, we represented the major events leading to antigen presentation by MHC class II molecules on APCs (e.g., macrophages) using ordinary differential equations (ODEs).…”

Section: Methodsmentioning

confidence: 99%

Effect of Multiple Genetic Polymorphisms on Antigen Presentation and Susceptibility toMycobacterium tuberculosisInfection

Chang¹,

Linderman

Kirschner

2008

Infect Immun

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Several molecules related to antigen presentation, including gamma interferon (IFN-␥) and the major histocompatibility complex (MHC), are encoded by polymorphic genes. Some polymorphisms were found to affect susceptibility to tuberculosis (TB) when they were considered singly in epidemiological studies, but how multiple polymorphisms interact to determine susceptibility to TB in an individual remains an open question. We hypothesized that polymorphisms in some genes may counteract or intensify the effects of polymorphisms in other genes. For example, an increase in IFN-␥ expression may counteract the weak binding that a particular MHC variant displays for a peptide from Mycobacterium tuberculosis to establish the same T-cell response as another, more strongly binding MHC variant. To test this hypothesis, we developed a mathematical model of antigen presentation based on experimental data for the known effects of genetic polymorphisms and simulated time courses when multiple polymorphisms were present. We found that polymorphisms in different genes could affect antigen presentation to the same extent and therefore compensate for each other. Furthermore, we defined the conditions under which such relationships could exist. For example, increased IFN-␥ expression compensated for decreased peptide-MHC affinity in the model only above a certain threshold of expression. Below this threshold, changes in IFN-␥ expression were ineffectual compared to changes in peptide-MHC affinity. The finding that polymorphisms exhibit such relationships could explain discrepancies in the epidemiological literature, where some polymorphisms have been inconsistently associated with susceptibility to TB. Furthermore, the model allows polymorphisms to be ranked by effect, providing a new tool for designing association studies.

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