Theres Matjeka

University College London

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Benny Chain

University College London

Mahdad Noursadeghi

University College London

James Heather

Weatherford College

Katharine Best

Merck & Co., Inc., Rahway, NJ, USA (United States)

John Shawe‐Taylor

University College London

José A. M. Borghans

University Medical Center Utrecht

Elizabeth Gray

Center for Drug Evaluation and Research

Dong Chen

Southeast University

Alice E. Denton

Imperial College London

Kiki Tesselaar

University Medical Center Utrecht

Cooperative Institutions

University College London

University of Oxford

Centre for Human Genetics

University of Cambridge

University Medical Center Utrecht

Swansea University

St George's, University of London

Cardiff University

Oxford BioMedica (United Kingdom)

Consejo Nacional de Investigaciones Científicas y Técnicas

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Changes in T cell receptor repertoire associated with combined variable immune-deficiency (CVID)

Mazlina Ismail Theres Matjeka Connor Husovsky James Heather Katharine Best

Common Variable Immunodeficiency

Immune receptor

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The immune system as a biomonitor: explorations in innate and adaptive immunity

Interface Focus (2013)

Niclas Thomas James Heather Gabriel Pollara Nandi Simpson Theres Matjeka

The human immune system has a highly complex, multi-layered structure which has evolved to detect and respond to changes in the internal microenvironment of the body. Recognition occurs at the molecular or submolecular scale, via classical reversible receptor–ligand interactions, and can lead to a response with great sensitivity and speed. Remarkably, recognition is coupled to memory, such that responses are modulated by events which occurred years or even decades before. Although the immune system in general responds differently and more vigorously to stimuli entering the body from the outside (e.g. infections), this is an emergent property of the system: many of the recognition molecules themselves have no inherent bias towards external stimuli (non-self) but also bind targets found within the body (self). It is quite clear that the immune response registers pathophysiological changes in general. Cancer, wounding and chronic tissue injury are some obvious examples. Against this background, the immune system ‘state’ tracks the internal processes of the body, and is likely to encode information regarding both current and past disease processes. Moreover, the distributed nature of most immune responses (e.g. typically involving lymphoid tissue, non-lymphoid tissue, bone marrow, blood, extracellular interstitial spaces, etc.) means that many of the changes associated with immune responses are manifested systemically, and specifically can be detected in blood. This provides a very convenient route to sampling immune cells. We consider two different and complementary ways of querying the human immune ‘state’ using high-dimensional genomic screening methodologies, and discuss the potentials of these approaches and some of the technological and computational challenges to be overcome.

10.1098/rsfs.2012.0099

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Chemical toxicity to keratinocytes triggers dendritic cell activation via an IL-1α path

Journal of Allergy and Clinical Immunology (2011)

Theres Matjeka Vicki Summerfield Mahdad Noursadeghi Benny Chain

Epidermis (zoology)

10.1016/j.jaci.2011.08.018

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Citations (6)

Poster Abstracts

Immunology (2014)

Zubair Ahmed Liset Westera Marjet Elemans Julia Drylewicz Yong Zhang

10.1111/imm.12406

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CD8α/α homodimers fail to function as co‐receptor for a CD8‐dependent TCR

European Journal of Immunology (2007)

Anne‐Marie McNicol Gavin Bendle Angelika Holler Theres Matjeka Emma Dalton

In this study, we have started to dissect the molecular basis of CD8 dependence of a high and low avidity CTL clone specific for the same peptide epitope. Using anti-CD8alpha and anti-CD8beta antibodies, we found that cytotoxicity and IFN-gamma production by high but not by low avidity CTL was strongly CD8 dependent. We isolated the TCR genes of both types of CTL clones and used retroviral gene transfer to analyse the function of these TCR in primary T cells of wild-type and CD8beta-deficient mice. Both TCR triggered antigen-specific killing in wild-type T cells, and blocking experiments showed that CD8 dependence/independence co-transferred with the TCR into primary T cells, indicating that it was dictated by the TCR itself. Gene transfer experiments into CD8beta-deficient T cells revealed that only the TCR derived from the CD8-independent CTL clone elicited antigen-specific cytotoxicity, while the CD8-dependent TCR was non-functional in the absence of the CD8beta-chain. These data indicate a striking difference between CD8alpha/beta heterodimers and CD8alpha/alpha homodimers as only the former were able to provide co-receptor function for the CD8-dependent TCR.

Avidity

CTL*

clone (Java method)

Adoptive Cell Transfer

10.1002/eji.200636900

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Citations (29)