Immune presentation: in the groove II.

The body depends on a few types of large proteins to determine whether substances are friend or foe. These proteins get their names from the genes that code for them - the major histocompatibility complex (MHC).

Last year, several research groups figured out how one class of these molecules, known as MHC-I proteins, binds to small pieces of protein and presents those pieces, called peptides, to the body's immune system (SN: 1/30/93, p.72).

On the basis of X-ray crystallographic data, researchers have now created this computer graphic. It snows that another type of MHC molecule, MHC-II, does a similar job but in a different way, says Lawrence J. Stern of the Howard Hughes Medical Institute (HHMI) at Harvard University Stern, HHMI's Don C Wiley, and their colleagues used genetically altered insect cells grown in the laboratory to make the MHC-II proteins and then added peptides copied from a flu virus protein to get a pure, easy-to-study protein-peptide complex.

Like an MHC-I protein, this MHC-II protein (in blue) binds to the peptide's backbone and contains pockets that can hold the side chains of the peptide's amino-acid building blocks. (Its carbon, nitrogen, and oxygen atoms are yellow, blue, and red, respectively) But this MHC groove contains specific amino acids (found in many organisms' MHC-II proteins) that make weak connections called hydrogen bonds along the length of the peptide rather than just grabbing the peptide at its ends, as MHC-I does. Thus, it can accommodate longer peptides than an MHC-I protein and even allow the ends to hang out of the binding site. This MHC-II molecule also has at least two more pockets for the peptide's side chains.

There's a reason for these differences, the researchers suggest in the March 17 NATURE. MHC-II molecules tend to attach to proteins coming from outside the cell and work alongside the cells machinery for processing this extracellular material. In contrast, MHC-I handles peptides created internally by the cell, Stern says.