title: Limited T cell receptor repertoire diversity in tuberculosis patients correlates with clinical severity.
abstract: BACKGROUND
  The importance of CD4⁺ and CD8⁺ T cells in protection against tuberculosis (TB) is well known, however, the association between changes to the T cell repertoire and disease presentation has never been analyzed. Characterization of T-cells in TB patients in previous study only analyzed the TCR β chain and omitted analysis of the Vα family even though α chain also contribute to antigen recognition. Furthermore, limited information is available regarding the heterogeneity compartment and overall function of the T cells in TB patients as well as the common TCR structural features of Mtb antigen specific T cells among the vast numbers of TB patients.
  
  
  RESULTS
  CDR3 spectratypes of CD4⁺ and CD8⁺ T cells were analyzed from 86 patients with TB exhibiting differing degrees of disease severity, and CDR3 spectratype complexity scoring system was used to characterize TCR repertoire diversity. TB patients with history of other chronic disease and other bacterial or viral infections were excluded for the study to decrease the likely contribution of TCRs specific to non-TB antigens as far as possible. Each patient was age-matched with a healthy donor group to control for age variability. Results showed that healthy controls had a normally diversified TCR repertoire while TB patients represented with restricted TCR repertoire. Patients with mild disease had the highest diversity of TCR repertoire while severely infected patients had the lowest, which suggest TCR repertoire diversity inversely correlates with disease severity. In addition, TB patients showed preferred usage of certain TCR types and have a bias in the usage of variable (V) and joining (J) gene segments and N nucleotide insertions.
  
  
  CONCLUSIONS
  Results from this study promote a better knowledge about the public characteristics of T cells among TB patients and provides new insight into the TCR repertoire associated with clinic presentation in TB patients.
authors.affiliation: Institute of Molecular Immunology, School of Biotechnology, Southern Medical University, Guangzhou, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Luo
authors.forename: Jin
authors.initials: J
authors.lastname: Su
authors.forename: Xiao-Bing
authors.initials: XB
authors.lastname: Zhang
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yang
authors.forename: Ming-Qian
authors.initials: MQ
authors.lastname: Zhou
authors.forename: Zhen-Min
authors.initials: ZM
authors.lastname: Jiang
authors.forename: Pei-Pei
authors.initials: PP
authors.lastname: Hao
authors.forename: Su-Dong
authors.initials: SD
authors.lastname: Liu
authors.forename: Qian
authors.initials: Q
authors.lastname: Wen
authors.forename: Qi
authors.initials: Q
authors.lastname: Jin
authors.forename: Li
authors.initials: L
authors.lastname: Ma
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000704:Analysis of Variance; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D022801:Complementarity Determining Regions / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005260:Female; D014644:Genetic Variation / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D012720:Severity of Illness Index; D014376:Tuberculosis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
chemical_list: D022801:Complementarity Determining Regions; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta