Skewed distribution of TCR V alpha 7-bearing T cells within tumor-infiltrating lymphocytes of HLA-A24(9)-positive patients with malignant glioma.
The identification and propagation of T cells with anti-tumor reactivity is critical for understanding the human immune response to tumors, which may possibly be useful in the successful implementation of adoptive immunotherapy against cancer. In order to address this question, we examined the diversity of mRNA transcripts of T-cell receptor (TCR) V alpha and V beta genes in tumor-infiltrating lymphocytes (TIL) of 12 glioma specimens obtained at surgery. Using the polymerase chain reaction (PCR) method and primers for 18 different human TCR V alpha and 22 V beta families to analyze TCR V-(D)-J-C gene rearrangements, we detected a limited expression of TCR variable region, V alpha genes and predominant usage of V alpha 7 within glioma TIL. TCR V beta gene usage was more diverse than that for V alpha, but TCR V beta 13.1 was dominantly expressed in 9 out of 12 patients. In addition, we analyzed the percentage of each V alpha- and V beta-bearing T-cell subpopulation in TIL as well as in peripheral blood lymphocytes (PBL) quantitatively. The distribution of T-cell subpopulation bearing each V alpha or V beta subfamily was variable and uneven in all cases. In 3 cases, the distribution of V alpha 7-bearing T cells in TIL was far higher than in PBL. This phenomenon was not found in T cells bearing TCR V beta 13.1. We also performed human leukocyte antigen (HLA) typing in these patients, and A24(9) was observed in 8 out of 11 patients. Among them all 3 patients who showed a skewed distribution of V alpha 7-bearing T cells in TIL expressed HLA-A24(9). There was no correlation between particular class I or II type and TCR V beta gene usage. From these results, it was strongly suggested that T cells bearing TCR V alpha 7 might be targeted to antigenic determinants on glioma cells, and such T-cell population may be useful as effector cells for cancer immunotherapy.
Ebato
M
M
Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan.
Nitta
T
T
Yagita
H
H
Sato
K
K
Okumura
K
K
D000328:Adult; D001483:Base Sequence; D001932:Brain Neoplasms / Q000235:genetics / Q000276:immunology*; D002675:Child, Preschool; D017931:DNA Primers; D005260:Female; D015870:Gene Expression; D005910:Glioma / Q000235:genetics / Q000276:immunology*; D015234:HLA-A Antigens / Q000276:immunology*; D059871:HLA-A24 Antigen; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012334:RNA, Neoplasm / Q000032:analysis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D017931:DNA Primers; D015234:HLA-A Antigens; D059871:HLA-A24 Antigen; D012334:RNA, Neoplasm; D016693:Receptors, Antigen, T-Cell, alpha-beta