Fine structural variations of alphabetaTCRs selected by vaccination with natural versus altered self-antigen in melanoma patients.

Immunotherapy of cancer is often performed with altered "analog" peptide Ags optimized for HLA class I binding, resulting in enhanced immunogenicity, but the induced T cell responses require further evaluation. Recently, we demonstrated fine specificity differences and enhanced recognition of naturally presented Ag by T cells after vaccination with natural Melan-A/MART-1 peptide, as compared with analog peptide. In this study, we compared the TCR primary structures of 1489 HLA-A*0201/Melan-A(26-35)-specific CD8 T cells derived from both cohorts of patients. Although a strong preference for TRAV12-2 segment usage was present in nearly all patients, usage of particular TRAJ gene segments and CDR3alpha composition differed slightly after vaccination with natural vs analog peptide. Moreover, TCR beta-chain repertoires were broader after natural than analog peptide vaccination. In all patients, we observed a marked conservation of the CDR3beta amino acid composition with recurrent sequences centered on a glycyl-leucyl/valyl/alanyl-glycyl motif. In contrast to viral-specific TCR repertoires, such "public" motifs were primarily expressed by nondominant T cell clonotypes, which contrasted with "private" CDR3beta signatures frequently found in T cell clonotypes that dominated repertoires of individual patients. Interestingly, no differences in functional avidity were observed between public and private T cell clonotypes. Collectively, our data indicate that T cell repertoires generated against natural or analog Melan-A peptide exhibited slightly distinct but otherwise overlapping and structurally conserved TCR features, suggesting that the differences in binding affinity/avidity of TCRs toward pMHC observed in the two cohorts of patients are caused by subtle structural TCR variations.

Testing the Tunnel Effect: Comparison, Age and Happiness in UK and German Panels

In contrast to previous results combining all ages we find positive effects of comparison income on happiness for the under 45s, and negative effects for those over 45. In the BHPS these coefficients are several times the magnitude of own income effects. In GSOEP they cancel to give no effect of effect of comparison income on life satisfaction in the whole sample, when controlling for fixed effects, and time-in-panel, and with flexible, age-group dummies. The residual age-happiness relationship is hump-shaped in all three countries. Results are consistent with a simple life cycle model of relative income under uncertainty.

Who is the fairest of them all? The independent effect of attractive features and self-perceived attractiveness on cooperation among women

The present paper analyzes the extent to which attractiveness-related variables affect cooperative behavior in women. Cooperativeness is evaluated through a Prisoner's Dilemma Game (PDG). We consider several morphometric variables related to attractiveness: Fluctuating Asymmetry (FA), Waist-Hip Ratio (WHR, Body Mass Index (BMI) and Facial Femininity (FF). These variables have been shown to predict human behavior. We also include as a control variable a score for Self-Perceived Attractiveness (SPA). We test differences in these variables according to behavior in the PDG. Our results reveal that low FA women cooperate less frequently in the PDG. We also find that women with lower WHR are more cooperative. This result contradicts the expected relation between WHR and behavior in the PDG. We show that this effect of WHR on cooperation operates through its influence on the expectation that participants hold on the cooperative intent of their counterpart. In addition, we show that the effect of attractive features on cooperation occurs independently of the participants' perception of their own appeal. Finally, we discuss our results in the context of the evolution of cooperative behavior and under the hypothesis that attractiveness is a reliable indicator of phenotypic quality.