The variations of TRBV genes usages in the peripheral blood of a healthy population are associated with their evolution and single nucleotide polymorphisms.

T cell receptors (TCRs) are a class of T cell surface molecules that recognize the antigen-derived peptides presented by the major histocompatibility complex (MHC) and are able to trigger a series of immune responses. TCRs are important members of the adaptive immune system that arose in the jawed fish 500 million years ago. T cell receptor beta variable (TRBV) genes have been widely used to characterize TCR repertoires. Studying the evolution of TRBV may help us to better understand the adaptive immune system. To investigate TRBV evolution and its impacts on the usages of TRBV genes in human populations, we compared the TRBV genes and their homologous sequences among humans, mouse, rhesus and chimpanzee, analyzed the single-nucleotide polymorphisms (SNPs) located at TRBV loci, and sequenced TCR repertoires in the peripheral blood of 97 healthy donors. We found that functional TRBVs are more evolutionarily conserved but possess more SNPs in human populations than do nonfunctional (pseudo) TRBVs. Based on the conservation levels in the four species, we classified the functional TRBVs into 2 groups: old (conserved between mouse and humans) and new (conserved only in primates). The new TRBVs evolve faster and possess more SNPs than the old TRBVs. The variations in TRBV genes frequencies in the peripheral blood of healthy donors are negatively correlated with SNP density. These observations suggest that TRBV usages may be influenced by TCR-MHC co-evolution.

[Responses of peginterferon-alpha 2a antiviral therapy in chronic hepatitis B patients].

OBJECTIVE: To study the responses of peginterferon-alpha 2a antiviral therapy in chronic hepatitis B (CHB) patients. METHODS: One hundred two CHB patients with their serum ALT values higher than 2x the upper limit of the normal (ULN) were divided into a HBeAg-positive and a HBeAg-negative group. All patients were treated with peginterferon-alpha 2a by subcutaneous injection (180 microgram once weekly). After treatment for 6 months, patients without a defined therapeutic response were dropped from the treatment group; the others completed a 12 month therapy. The sustained response and the antiviral effect of the treatment were assessed at the end of the therapy. To investigate the possible impact factors of the response to peginterferon-alpha 2a, we studied the therapeutic response of patients with different serum ALT levels, inflammation grades of liver histology, stages of fibrosis, and HBV viral load levels. RESULTS: (1) There was no statistical difference of the rates of response at the end of treatment and 6, 12, 18, 24 and 30 months after the cessation of therapy between the HBeAg-positive and the HBeAg-negative groups. (2) In the HBeAg-positive group, the rates of response of patients with serum ALT values>3*ULN were significantly higher than those with serum ALT values less than 3*ULN (x2=4.40). However, no statistical difference of serum ALT levels was found in the HBeAg-negative group. (3) In both HBeAg-positive and HBeAg-negative groups, no difference was revealed in the rates of response among patients with different levels of HBV viral loads. (4) In the HBeAg-positive group, patients with more severe liver inflammation histologically (G3 and G4) had significantly higher response rates than those with milder inflammation (G1 and G2) (x2=4.19), but no similar statistical differences were found in the HBeAg-negative group. Moreover, there was no difference in the rates of response among patients in different stages of liver fibrosis in both HBeAg-positive and HBeAg-negative groups. CONCLUSIONS: Similar rates of response and sustained virological response to the peginterferon-alpha 2a treatment can be achieved in both HBeAg-positive and HBeAg-negative patients. Hepatic fibrosis is not a predictor of poor therapeutic response. For HBeAg-positive patients, more severe liver inflammation identified with liver biopsies (G3 or G4) and high serum ALT values (more than 3*ULN) can be considered as predictors of a good therapeutic response.