Dr. Mariuzza's Research Group Finding Selected by F1000

Researchers in the laboratory of Dr. Roy Mariuzza, at the University of Maryland Institute of Bioscience and Biotechnology Research (IBBR) and Department of Cell Biology and Molecular Genetics (CBMG), have developed unique tools for probing the influence of the interaction of immune cell receptors CD4 and MHC class II on T-cell activation and development. The group published the findings, titled “Affinity maturation of human CD4 by yeast surface display and crystal structure of a CD4–HLA-DR1 complex”, in the September 10 issue of PNAS. While it is known that helper T-cell activation generally requires CD4 binding to MHC class II molecules, previous efforts to define the CD4–MHC class II interaction at the atomic level have been quite difficult due to its exceptionally low affinity. Using in vitro-directed evolution, the research group was able to isolate a CD4 mutant with increased affinity for the human class II molecule HLA-DR1. The resulting complex provided a much more detailed picture of how CD4 recognizes MHC molecules than previously published low-resolution structures. This work may enable researchers to further determine the structure of a complete ternary complex of T cell receptor, MHC class II, and CD4.

This paper was also selected and evaluated by Dr. Jia-huai Wang, a Member of the Faculty of 1000 (F1000), which places the work in a library of the top 2% of published articles in biology and medicine. The F1000 evaluates the most important articles in biology and medical research publications. Articles published in the field are selected by a 'Faculty' of world-leading scientists and clinicians who then rate them and explain their importance.

The work in the Mariuzza lab at IBBR is internationally recognized for advances in structural immunology. The overall focus of the lab is the understanding the molecular basis of ligand recognition by cell surface receptors of the immune system. Several classes of recognition molecules are under study, including antibodies, T cell receptors, natural killer cell receptors, and variable lymphocyte receptors.