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Nucleic Acids Research, 2003, Vol. 31, No. 22 e139
© 2003 Oxford University Press

Article

Direct measurement of lymphocyte receptor diversity

Brenda M. Ogle1,2, Marilia Cascalho1,3,4, Cristina Joao1, William Taylor5, Lori J. West7 and Jeffrey L. Platt*,1,3,4,6

1 Transplantation Biology Program, 2 Department of Physiology, 3 Department of Immunology, 4 Department of Pediatrics, 5 The Cancer Center and 6 Department of Surgery, Mayo Clinic, Rochester, Minnesota, MN 55905, USA and 7 The Hospital for Sick Children Research Institute and the University of Toronto, Toronto, ON, Canada

*To whom correspondence should be addressed at Mayo Clinic, Transplantation Biology, 200 First Street SW, Medical Sciences 2-66, Rochester, MN 55905, USA. Tel: +1 507 538 0313; Fax: +1 507 284 4957; Email: platt.jeffrey{at}mayo.edu

The ability to mount an immune defense against infectious microorganisms and their products, and against tumors is believed to be a direct function of lymphocyte diversity. Because the diversity of lymphocyte receptor genes is >1000-fold more diverse than the entire genome and varies between genetically identical individuals, measuring lymphocyte diversity has been a daunting challenge. We developed a novel technique for measuring lymphocyte diversity directly using gene chips. We reasoned and here demonstrate that the frequency of hybridization of nucleic acids coding for lymphocyte receptors to the oligonucleotides on a gene chip varies in direct proportion to diversity. We applied the technique to detect changes in lymphocyte diversity in mice with known B cell alterations and in persons with known T cell repertoire defects. This approach is the first to provide direct analysis of lymphocyte receptor diversity and should facilitate fundamental study of the adaptive immune system and clinical efforts to assess immunological diseases. In addition, this approach could be more broadly applied, for example to measure diversity of viral quasi-species.


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