Clinical immunological and immunogenetical aspects of neurological diseases.

The anti-tumor response of human invariant NKT (NKT) cells is well established. A novel T cell subset, mucosal-associated invariant T (MAIT) cells, possesses similar regulatory properties to NKT cells in autoimmune models and disease. Here, we examined the clonality of four T cell subsets expressing invariant aTCR, including Va7.2-Ja33 of MAIT cells, in 19 kidney and brain tumors. The MAIT clonotype was identified and co-expressed with NKT clonotype in half of the tumors. In contrast, two other invariant T cell clonotypes (Va4 and Va19) were not present in tumors. Such tumors also expressed Vb2 and Vb13, the restricted TCRb chain of MAIT cells and the antigen-presenting molecule MR1. A high percentage of infiltrating T cells was CD81 and expressed HLA-DR suggesting activation. Although the MAIT aTCR was identified in both peripheral CD561 and CD562 subsets, infiltrating lymphocytes were CD56 negative. The clonal presence of MAIT cells in tumors correlated with the expression of pro-inflammatory cytokines but no IL-4, IL-5 and IL-10, suggesting that a proinflammatory subset of human MAIT cells may exist. Our data imply that a CD562 subset of MAIT cells may participate in tumor immune responses similarly to NKT cells. Introduction The heterogeneous T cell repertoire of mainstream lymphocytes is generated by random recombination of V, D and J segments and junctional deletion and insertion of nucleotides. In contrast, innate lymphocytes are characterized by limited repertoire diversity. The best-characterized invariant abT cell population, NKT cells, was identified in the early 90s in humans (1, 2). NKT cells express the invariant Va24JaQ CDR3 and reside mostly in the CD4ÿCD8ÿ (double negative (DN)) and CD4+ cell subsets (1, 2). The CD1d recognition of DN Va24 T cells and the restricted Vb usage defined this subset as the human analog of murine NKT cells (3, 4). Emerging data indicate the functional diversity of human NKT cells and their involvement in tumor immunity and autoimmunity (5–8). Along with the identification of Va24 NKT cells, another DN T cell population expressing an invariant Va7.2-Ja33 TCR has been described (1). Homologous TCR sequences displaying the same CDR3 length could be identified in bovine and murine DN T cell subsets (Va19.1-Ja26), suggesting an important physiological function (9). Out of the two TCAV7 genes, most of the conserved Va7+ clones utilize the AV7.2 gene segment in humans (10–12). In addition to the conserved CDR3a, mucosal-associated invariant T (MAIT) cells express a restricted Vb2 and Vb13 driven by the selecting antigen (9, 10). The preferential location of invariant Va7.2-Ja33 T cells is the gut lamina propria; hence, the name MAIT cells has been recently suggested (13). Nevertheless, MAIT cells are also present in the peripheral blood at a similar frequency to Va24 NKT cells (0.1–0.2%) and constitute about up to 15% of DN T cells (10). Va7.2-Ja33 MAIT cells are selected by a non-classical MHC class Ib molecule, MR1 encoded by chromosome 1, similarly to CD1d. Several lines of evidence suggest that MR1 presents ligands to MAIT cells, possibly glycolipids, similarly to NKT cells (13–16). Recent data suggest that MAIT cells are similar to NKT cells in a number of aspects: both use a semi-invariant TCR, recognize glycolipids and are activated in a co-receptorindependent manner, selected and restricted by a monomorphic class I-like molecule and characterized by a natural memory phenotype, suggesting a high-avidity interaction with Correspondence to: Z. Illes; E-mail: [email protected] Transmitting editor: A. Falus Received 2 June 2008, accepted 12 September 2008 International Immunology Advance Access published October 16, 2008