Invariant Valpha7.2-Jalpha33 TCR is expressed in human kidney and brain tumors indicating infiltration by mucosal-associated invariant T (MAIT) cells

• Published in: International immunology 2008-12, Vol.20 (12), p.1517-1525
• Main Authors: Peterfalvi, Agnes, Gomori, Eva, Magyarlaki, Tamas, Pal, Jozsef, Banati, Miklos, Javorhazy, Andras, Szekeres-Bartho, Julia, Szereday, Laszlo, Illes, Zsolt
• Format: Article
• Language: English
• Subjects: Brain Neoplasms - genetics; Brain Neoplasms - metabolism; Brain Neoplasms - pathology; Carcinoma, Renal Cell - genetics; Carcinoma, Renal Cell - metabolism; Carcinoma, Renal Cell - pathology; CD56 Antigen - biosynthesis; CD56 Antigen - genetics; Cell Separation; Cytokines - secretion; Flow Cytometry; Gene Expression - immunology; Genes, T-Cell Receptor alpha - immunology; Glioblastoma - genetics; Glioblastoma - metabolism; Glioblastoma - pathology; HLA-DR Antigens - biosynthesis; HLA-DR Antigens - genetics; Humans; Immunity, Mucosal; Immunohistochemistry; Kidney Neoplasms - genetics; Kidney Neoplasms - metabolism; Kidney Neoplasms - pathology; Lymphocyte Activation; Lymphocytes, Tumor-Infiltrating - metabolism; Meningeal Neoplasms - genetics; Meningeal Neoplasms - metabolism; Meningeal Neoplasms - pathology; Meningioma - genetics; Meningioma - metabolism; Meningioma - pathology; Natural Killer T-Cells - metabolism; Polymorphism, Single-Stranded Conformational; T-Lymphocyte Subsets - metabolism
• ISSN: 1460-2377
• DOI: 10.1093/intimm/dxn111

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 alphaTCR, including Valpha7.2-Jalpha33 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 (Valpha4 and Valpha19) were not present in tumors. Such tumors also expressed Vbeta2 and Vbeta13, the restricted TCRbeta chain of MAIT cells and the antigen-presenting molecule MR1. A high percentage of infiltrating T cells was CD8+ and expressed HLA-DR suggesting activation. Although the MAIT alphaTCR was identified in both peripheral CD56+ and CD56- 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 pro-inflammatory subset of human MAIT cells may exist. Our data imply that a CD56- subset of MAIT cells may participate in tumor immune responses similarly to NKT cells.