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Revisiting the T-cell receptor alpha/delta locus and possible associations with multiple sclerosis

Genes & Immunity volume 12, pages 59–66 (2011)Cite this article

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Abstract

A role for T cells in the pathogenesis of multiple sclerosis (MS) is well supported, evidenced by myriad immunological studies, as well as the unequivocal genetic influence of the major histocompatibility complex (MHC). Despite many attempts, no convincing genetic associations have been made between T-cell receptor (TCR) gene loci and MS. However, these studies may not be definitive because of small sample sizes and under-representative marker coverage of the chromosomal regions being investigated. To explore potential roles between the TCR alpha locus and MS, we have genotyped a large family-based cohort, including 1360 affected individuals and 1659 of their unaffected first-degree relatives, at 40 single-nucleotide polymorphism (SNP) markers within the TCR alpha/delta locus. This represents the largest TCR alpha-MS study to date. From this screen, we identified three potential loci of interest in TCR alpha variable and constant gene regions using the transmission disequilibrium test. Although SNPs implicating each of these regions of interest will require genotyping in independent replication cohorts, these findings suggest a role for TCR gene polymorphisms in MS susceptibility. In the context of these findings we review the evidence.

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Acknowledgements

This study was supported by the Multiple Sclerosis Society of Canada Scientific Research Foundation, the Multiple Sclerosis Society of Great Britain and Northern Ireland and the Natural Sciences and Engineering Research Council of Canada. We thank all patients who generously participated in this study and physicians participating in the CCPGSMS. Experiments performed for this investigation comply with current guidelines and ethics.

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  1. C T Watson and A E Para: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Biological Sciences, Simon Fraser University, Burnaby, British Columbia, Canada

    C T Watson & F Breden

  2. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK

    A E Para, M R Lincoln, S V Ramagopalan, S M Orton, K M Morrison, L Handunnetthi, A E Handel, M J Chao, J Morahan & G C Ebers

  3. Department of Clinical Neurology, University of Oxford, The West Wing, John Radcliffe Hospital, Oxford, UK

    M R Lincoln, S V Ramagopalan, S M Orton, L Handunnetthi, A E Handel, M J Chao, J Morahan & G C Ebers

  4. Blizard Institute of Cell and Molecular Science, Queen Mary University of London, Barts and The London School of Medicine and Dentistry, London, UK

    S V Ramagopalan

  5. Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada

    A D Sadovnick

  6. Division of Neurology, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada

    A D Sadovnick

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  1. C T Watson
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  2. A E Para
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  3. M R Lincoln
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Correspondence to F Breden or G C Ebers.

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Watson, C., Para, A., Lincoln, M. et al. Revisiting the T-cell receptor alpha/delta locus and possible associations with multiple sclerosis. Genes Immun 12, 59–66 (2011). https://doi.org/10.1038/gene.2010.65

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