Immune mechanisms of protection: can adjuvants rise to the challenge?

For many diseases vaccines are lacking or only partly effective. Research on protective immunity and adjuvants that generate vigorous immune responses may help generate effective vaccines against such pathogens

Yeast Surface Display of a Noncovalent MHC Class II Heterodimer Complexed with Antigenic Peptide

Microbial protein display technologies have enabled directed molecular evolution of binding and stability properties in numerous protein systems. In particular, dramatic improvements to antibody binding affinity and kinetics have been accomplished using these tools in recent years. Examples of successful application of display technologies to other immunological proteins have been limited to date. Herein, we describe the expression of human class II major histocompatibility complex allele (MHCII) HLA-DR4 on the surface of Saccharomyces cerevisiae as a noncovalently associated heterodimer. The yeast-displayed MHCII is fully native as assessed by binding of conformationally specific monoclonal antibodies; failure of antibodies specific for empty HLA-DR4 to bind yeast-displayed protein indicates antigenic peptide is bound. This report represents the first example of a noncovalent protein dimer displayed on yeast and of successful display of wildtype MHCII. Results further point to the potential for using yeast surface display for engineering and analyzing the antigen binding properties of MHCII

Bax does not have to adopt its final form to drive T cell death

The introduction of antigen into animals causes antigen-specific T cells to divide and then die. Activated T cell death requires either of the death effector molecules, Bak or Bax. When T cells die, Bak and Bax change their conformations, a phenomenon that is thought to be required for Bak or Bax to drive cell death. Here we show that Bak changes conformation before activated T cells die, as detected by an antibody specific for a peptide near the NH2 terminus of Bak, but Bax does not change its shape markedly until after the cells are dead, as detected by an antibody specific for a peptide near the NH2 terminus of Bax. This latter finding is also true in activated T cells that lack Bak and are therefore dependent on Bax to die. This result suggests that Bax does not have to adopt its final, completely unfolded form until after the cells are dead