Alterations in T-Cell Receptor Vβ Repertoire of CD4 and CD8 T Lymphocytes in Human Immunodeficiency Virus-Infected Children

Abstract

Perturbations in the T-cell receptor (TCR) V␤ repertoire were assessed in the CD4 and CD8 T lymphocytes of human immunodeficiency virus (HIV)-infected children who were receiving therapy during the chronic phase of infection by flow cytometry (FC) and PCR analysis. By FC, representation of 21 TCR V␤ subfamilies was assessed for an increased or decreased percentage in CD4 and CD8 T cells, and by PCR, 22 TCR V␤ subfamilies of CD4 and CD8 T cells were analyzed by CDR3 spectratyping for perturbations and reduction in the number of peaks, loss of Gaussian distribution, or clonal dominance. The majority of the TCR V␤ subfamilies were examined by both methods and assessed for deviation from the norm by comparison with cord blood samples. The CD8-T-lymphocyte population exhibited more perturbations than the CD4 subset, and clonal dominance was present exclusively in CD8 T cells. Of the 55 total CD8-TCR V␤ families classified with clonal dominance by CDR3 spectratyping, only 18 of these exhibited increased expression by FC. Patients with high numbers of CD8-TCR V␤ families with decreased percentages had reduced percentages of total CD4 T cells. Increases in the number of CD4-TCR V␤ families with increased percentages showed a positive correlation with skewing. Overall, changes from normal were often discordant between the two methods. This study suggests that the assessment of HIV-induced alterations in TCR V␤ families at cellular and molecular levels yields different information and that our understanding of the immune response to HIV is still evolving.The majority of peripheral blood CD4 and CD8 T cells express the ␣␤ T-cell receptor (TCR), with the ␤ chain represented by variable segments which are grouped into families based on sequence homology (16). A complete T-cell repertoire is indicative of an intact T-cell population with the potential to recognize a wide range of immunogens. Numerous reports have documented changes in the TCR V␤ repertoire during human immunodeficiency virus (HIV) infection in relation to disease progression and the effect of therapy (4,5,(8)(9)(10)(19)(20)(21)(22)(23). CDR3 length spectratyping (8,19,21) and flow cytometric (FC) analysis of TCR V␤ families labeled with specific monoclonal antibodies (MAbs) (4,7,26) are among the most frequently used assays for the analysis of TCR V␤ repertoire in HIV infection. The CDR3 spectratype is an indicator of the relative proportion of cells in each TCR V␤ family with CDR3 of particular lengths, while labeling of cells with TCR-V␤-specific MAbs provides a quantitative assessment of the percentages of particular TCR V␤ families in T cells. Thus, evaluation of the TCR V␤ repertoire with MAbs, in combination with CDR3 spectratyping, is expected to provide complementary information. In the present study, we analyzed the TCR V␤ repertoire in the CD4 and CD8 T cells of 22 HIV-infected children by CDR3 length analysis and by FC. MATERIALS AND METHODSPatient population. TCR V␤ repertoire analyses by PCR and FC were performed concurrently in 22 HIV-infected c...

Role of TLR4 and TCR or BCR against baicalin-induced responses in T and B cells

“…In recent years, it was found that some cytokines can integrate with TCR Vβ to activate T cells even without the aid of MHC-II molecules. It was also found that increasing TCR Vβ mRNA expression helped activate T cells in anti-infection immunity, promote cytotoxic effects of CD8 + T cells and stimulate antiviral cytokine secretion [24][25]. The B cell receptor (BCR) is also called membrane immunoglobulin (mIg), and is a characteristic surface marker of B cells.…”

T cell receptor Vβ repertoire of T lymphocytes and T regulatory cells by flow cytometric analysis in healthy children

“…The majority of peripheral blood T lymphocytes express the ab-TCR receptor comprising a heterodimer of a-and b-chains. A complete TCR repertoire is indicative of an intact T cell population with the ability to recognize a wide range of immunogens [2].…”

Characterization of the T-Cell Receptor Vβ Repertoire in the Human Immune Response againstLeishmaniaParasites

“…T cells recognize foreign antigens through T-cell antigen receptors (TCRs), and diversity in antigen recognition is generated by ␣ and ␤ genes that rearrange randomly in differentiating T cells. In this sense, the study of the TCR repertoire may contribute to the understanding of disease pathogenesis and, for this reason, has been an important focus of research in several diseases (16,22,31,35,37,38,53). Either PCR-based methods (14,46,47) or flow cytometry using TCR V␤-specific monoclonal antibodies (5,8,15,27) has been employed to analyze the expression of TCR ␣ and ␤ variable genes.…”