Molecular characterization of the T cell repertoire using immunoscope analysis and its possible implementation in clinical practice

F. Ria, P. Van Den Elzen, L. T. Madakamutil, J. E. Miller, Emanual Michael Maverakis, E. E. Sercarz

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

T lymphocytes play a central role in the pathogenesis of a large number of human conditions including autoimmunity and graft rejection. Although T cells are key players in mounting immune responses, the assessment of T cell repertoires has yet to find an important role in clinical decision making. In this review, we discuss the "immunoscope" technique and its potential diagnostic role in a variety of clinical scenarios. This is an RT-PCR based approach that subdivides a bulk T cell population (i. e. from blood, lymph, spleen, or tissue) into approximately 2800 groups based upon rearranged variable beta (Vβ)/joining beta (Jβ) gene segments and the resulting length of the T cell receptor's (TCR's) third complementarity determining region (CDR-3). This extensive subdivision, or focusing, allows clonal expansions to be directly observed. Such a fine-tuned analysis has revealed previously unappreciated aspects of the T cell repertoire. For instance, an antigen-specific immune response can be divided into both public and non-public components. The non-public repertoire contains the majority of the expanding T cells which are unique to the individual (private), or shared by only some (semi-private), while "public" T cells can be found responding to the antigenic determinant in every individual. Although they are often a minority of the response, the public T cell repertoire seems to play a more important role in defining, as well as driving, the overall immune phenotype in the animal. Immunoscope analysis has identified public and non-public responses in human pathologies, such as multiple sclerosis. The ability to characterize the driver T cells dictating the state of immunity/autoimmunity in individual patients will be an important step towards understanding autoimmunity and designing effective treatment for a variety of conditions including rheumatoid arthritis and multiple sclerosis. We review the current literature involving public and non-public repertoires and discuss the prospect that immunoscope analysis may play a central role in the study and perhaps the management of human autoimmune diseases, and cancer. Key words: autoimmunity, arthritis, cancer, driver clones, self, TCR, tolerance, spectratyping, EAE, Multiple Sclerosis.

Original languageEnglish (US)
Pages (from-to)297-304
Number of pages8
JournalCurrent Molecular Medicine
Volume1
Issue number3
StatePublished - 2001

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T-cells
T-Lymphocytes
Autoimmunity
Multiple Sclerosis
Complementarity Determining Regions
T-Cell Antigen Receptor
Histocompatibility Antigens Class II
Graft Rejection
Lymph
Pathology
Mountings
Grafts
Joining
Autoimmune Diseases
Arthritis
Epitopes
Immunity
Rheumatoid Arthritis
Neoplasms
Animals

ASJC Scopus subject areas

  • Biochemistry

Cite this

Molecular characterization of the T cell repertoire using immunoscope analysis and its possible implementation in clinical practice. / Ria, F.; Van Den Elzen, P.; Madakamutil, L. T.; Miller, J. E.; Maverakis, Emanual Michael; Sercarz, E. E.

In: Current Molecular Medicine, Vol. 1, No. 3, 2001, p. 297-304.

Research output: Contribution to journalArticle

Ria, F. ; Van Den Elzen, P. ; Madakamutil, L. T. ; Miller, J. E. ; Maverakis, Emanual Michael ; Sercarz, E. E. / Molecular characterization of the T cell repertoire using immunoscope analysis and its possible implementation in clinical practice. In: Current Molecular Medicine. 2001 ; Vol. 1, No. 3. pp. 297-304.
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