Molecular Characterization of the T Cell Repertoire Using Immuno-scope Analysis and its Possible Implementation in Clinical Practice

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 (Vbeta)/joining beta (Jbeta) 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.

Timely DNA Vaccine Combined with Systemic IL-12 Prevents Parotid Carcinomas before a Dominant-Negative p53 Makes Their Growth Independent ofHER-2/neuExpression

“…This absence is not surprising, because HER-2 transgenic mice express r-HER-2 in the thymus, and central and peripheral tolerance takes place (41,42). Spectratyping (43) showed that central tolerance in transgenic BALB-neuT and BALB-neuT/p53…”

Vitamin C Promotes Maturation of T-Cells

“…To further characterize the expression and diversity of rearranged TCR molecules in lymphocytes maturing in OP9-DL1 cultures, we utilized immunoscope analysis (23) (Fig. 7A).…”

Unique Gene Expression Patterns in Human T‐cell Lines Generated from Multiple Sclerosis Patients by Stimulation with a Synthetic MOG Peptide

“…The analysis was performed according to the analytical approach as previously described (LovettRacke et al 1998, Ben-Dor et al 2000, Ria et al 2001. Fold ratios were calculated for each gene of the samples against the geometric mean of matched controls.…”

“…Although, T-cell lines derived from MS patients and healthy donors responded to the same autoantigen, the gene expression imprints that are unique to each group were preserved. The nature of the stimuli that generate aberrant autoimmune T-cell gene expression has yet to be identified in order to determine whether their formation is merely the result of the chronic immune stimulation driven by other factors in MS, or whether such T-cells function are the primary drivers of the pathogenic MS process (Ria et al 2001). On the other hand, the difference we demonstrated between autoreactive T-cells in patients and healthy subjects suggests that though both are activated and against the same myelin antigen their state is different, and the change in state is of importance.…”