JOURNAL OF BIOLOGICAL REGULATORS & HOMEOSTATIC AGENTS Vol. 25, no. 2, 0-0 (2011) 0393-974X (2011) Copyright © by BIOLIFE, s.a.s. This publication and/or article is for individual use only and may not be further reproduced without written permission from the copyright holder. Unauthorized reproduction may result in financial and other penalties 153 Mature T-lymphocytes recognize antigens through a highly specialized molecule: a hypervariable heterodimer referred to as the T-cell receptor (TCR). The diversity of the TCR variability repertoire is the result of gene recombination among a series of variable (V) region genes in combination with diversity (D) and joining (J) region segments. In addition, the complementary determining region 3 (CDR3) portion of the beta-chain adds additional fine specificity to the TCR, rendering the TCR unique for each T-cell. The majority of T-cells expresses the alpha-beta TCR, while a minority (about 5%) of cells expresses an alternative gamma-delta receptor (1). In normal peripheral blood lymphocytes TCR repertoire is usually polyclonal. However, in malignancies such as leukemias,(2), as well as in lymphoproliferative diseases of mature T-cells (3- 5), the TCR is a reflection of the clonality of the malignant cells and is therefore monoclonal (6). The ability to study TCR repertoire dates back to the last decades of the 20 th century, first using the Southern blot technique and later with the more sensitive TCR spectratyping. With these techniques it became evident that in non-leukemic diseases, including solid and haematological neoplasias, auto-immune disorders, infectious diseases and allergic diseases, T-cells responding to diverse stimuli and infiltrating tissues of every organ may express a skewed or EDITORIAL SKEWED T-CELL RECEPTOR REPERTOIRE: MORE THAN A MARKER OF MALIGNANCY, A TOOL TO DISSECT THE IMMUNOPATHOLOGY OF INFLAMMATORY DISEASES F. PANDOLFI 1 , R. CIANCI 1 , F. CASCIANO 1 , D. PAGLIARI 1 , T. DE PASQUALE 1 , R. LANDOLFI 1 , G. DI SANTE 2 , J.T. KURNICK 3 and F. RIA 2 1 Department of Internal Medicine and 2 General Pathology Catholic University, Rome, Italy; 3 Harvard Medical School and the Massachusetts General Hospital, Boston, Ma. USA Received February 2, 2010 – Accepted April 15, 2011 The highly diverse heterodimeric surface T cell receptor (TCR) gives the T lymphocyte its specificity for MHC-bound peptides needed to initiate antigen-recognition. In normal peripheral blood, spleen and lymph nodes, the TCR repertoire of the T lymphocytes is usually polyclonal. However, in malignancies such as leukemias, as well as in lymphoproliferative diseases of mature T cells, the TCR is a reflection of the clonality of the malignant cells and is therefore monoclonal. Several clinical conditions (mainly solid tumors and autoimmune diseases) have been described where the TCR repertoire is restricted. The ability to demonstrate clonal TCR usage provides a useful tool to dissect the immunopathology of inflammatory diseases. In this review we discuss these findings and propose to sub-divide diseases with restricted TCR repertoire into a group of conditions in which there is a known TCR ligand, as opposed to diseases in which the restricted TCR repertoire is the result of impaired T-cell development. This classification sheds light on the pathogenesis of several inflammatory diseases. Mailing address: Prof. Francesco Ria, Istituto di Patologia Generale, Universita’ Cattolica, Largo F. Vito, 1 00168 Rome, Italy Tel: ++39 0630164914 Fax: ++39 063386446 e-mail: fria@rm.unicatt.it Key words: T-cell receptor, solid tumors melanoma, autoimmune diseases, skewed TCR repertoire, spectratyping, rheumatoid arthritis