- A highly focused antigen receptor repertoire characterizes gamma delta T cells that are poised to make IL-17 rapidly in naive animals FRONTIERS IN IMMUNOLOGY 2015; 6: 1-6
- Linking T-cell receptor sequence to functional phenotype at the single-cell level NATURE BIOTECHNOLOGY 2014; 32 (7): 684-?
Linking T-cell receptor sequence to functional phenotype at the single-cell level.
2014; 32 (7): 684-692
Although each T lymphocyte expresses a T-cell receptor (TCR) that recognizes cognate antigen and controls T-cell activation, different T cells bearing the same TCR can be functionally distinct. Each TCR is a heterodimer, and both α- and β-chains contribute to determining TCR antigen specificity. Here we present a methodology enabling integration of information about TCR specificity with information about T cell function. This method involves sequencing of TCRα and TCRβ genes, and amplifying functional genes characteristic of different T cell subsets, in single T cells. Because this approach retains information about individual TCRα-TCRβ pairs, TCRs of interest can be expressed and used in functional studies, for antigen discovery, or in therapeutic applications. We apply this approach to study the clonal ancestry and differentiation of T lymphocytes infiltrating a human colorectal carcinoma.
View details for DOI 10.1038/nbt.2938
View details for PubMedID 24952902
- Dietary gluten triggers concomitant activation of CD4(+) and CD8(+) alpha beta T cells and gamma delta T cells in celiac disease PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2013; 110 (32): 13073-13078
Virus-Specific CD4(+) Memory-Phenotype T Cells Are Abundant in Unexposed Adults
2013; 38 (2): 373-383
Although T cell memory is generally thought to require direct antigen exposure, we found an abundance of memory-phenotype cells (20%-90%, averaging over 50%) of CD4(+) T cells specific to viral antigens in adults who had never been infected. These cells express the appropriate memory markers and genes, rapidly produce cytokines, and have clonally expanded. In contrast, the same T cell receptor (TCR) specificities in newborns are almost entirely naïve, which might explain the vulnerability of young children to infections. One mechanism for this phenomenon is TCR cross-reactivity to environmental antigens, and in support of this, we found extensive cross-recognition by HIV-1 and influenza-reactive T lymphocytes to other microbial peptides and expansion of one of these after influenza vaccination. Thus, the presence of these memory-phenotype T cells has significant implications for immunity to novel pathogens, child and adult health, and the influence of pathogen-rich versus hygienic environments.
View details for DOI 10.1016/j.immuni.2012.10.021
View details for Web of Science ID 000330940800018
View details for PubMedID 23395677
The promised land of human immunology.
Cold Spring Harbor symposia on quantitative biology
2013; 78: 203-213
Advances in technology and data analysis have made it possible to take a new look at human immunology. These advances run the gamut from systems biology approaches, which are likely in the vanguard of how we can start "to put the pieces together" of immune function, to a deeper understanding of specific diseases and vaccines and the immune repertoire. In our own experience, we have also found that asking simple questions about human immunity has often given us very surprising answers, causing a rethink of established dogma. Thus, we have developed a new perspective on the nature of the αβ TCR repertoire and also the likely role of T-cell repertoire (TCR) cross-reactivity in generating T memory independent of specific antigen interactions. These findings show that human immunology is not just a necessary step for "translating" basic immunology to treat diseases or develop better vaccines, but is also an important complement to the inbred mouse model.
View details for DOI 10.1101/sqb.2013.78.022905
View details for PubMedID 24638855