Proceedings of the National Academy of Sciences of the United States of America

About the PNAS Member Editor
Name Cresswell, Peter
Location Yale University
Primary Field Immunology and Inflammation
Secondary Field Biochemistry
 Election Citation
Cresswell fine-tuned our understanding of the molecular steps needed for antigens to trigger an immune response by T white blood cells. His research revealed the intricate assembly and intracellular transport of the major histocompatibility complex molecules, as well as how antigens are processed so that they lodge within these molecules for T-cell recognition.
 Research Interests
My major interest is in antigen processing, defined as the combination of mechanisms that generate the complexes of class I and class II MHC molecules with peptides that are the targets for recognition by T lymphocytes. My colleagues and I have identified a number of proteins that collaborate in these processes. MHC class I peptide binding occurs in the context of a large complex that we have defined in the endoplasmic reticulum consisting of TAP, an ATP-dependent peptide transporter; tapasin, a protein that couples the transporter to assembling class I molecules; and two "house-keeping" chaperones, calreticulin and ERp57. How these accessory molecules combine to facilitate peptide binding is currently being intensively investigated. We have also studied MHC class II peptide binding through the mechanism of class II molecules being delivered into the endocytic pathway by an associated protein, the invariant chain. This has included study of the CLIP, a residual fragment of the invariant chain, and the catalysis actions of a related protein called DM. Recently, we also identified a thiol reductase called GILT, which facilitates the generation of class II-binding peptides from protein antigens rich in disulfide bonds.

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