Peter Cresswell, Ph.D.

Professor of Immunobiology and Cell Biology and Dermatology Investigator, Howard Hughes Medical Institute
Cresswell lab website Phone: (203) 785-5176 Lab: (203) 737-2452 Assistant: (203) 785-5176 Fax: (203) 785-4461 e-mail: peter.cresswell@yale.edu		Section of Immunobiology Yale University School of Medicine 300 Cedar Street P.O. Box 208011 New Haven, CT 06520-8011 <Courier Address> 300 Cedar Street, TAC S669/670 New Haven, CT 06519-1612

The major interest of this laboratory is in the mechanisms regulating antigen processing. MHC class I molecules in the endoplasmic reticulum (ER) bind peptides translocated from the cytosol by the Transporters associated with Antigen Processing (TAP). The assembly of a class I-ß2 microglobulin dimer involves two chaperones, calnexin and calreticulin, and the thiol oxido-reductase, ERp57. Calreticulin- and ERp57-associated class I molecules physically associate with TAP molecules, with an MHC encoded glycoprotein, tapasin, serving as a bridge. The functions of this complex are currently under investigation.

MHC class II molecules form a nine chain complex in the ER, with three a-b dimers associated with a trimer of the invariant chain. After invariant chain degradation in the endocytic pathway, a residual invariant chain fragment is catalytically eliminated by an MHC-encoded glycoprotein, HLA-DM, liberating the peptide binding site of the class II molecule. Peptides or large fragments of protein can bind and reduction of protein disulfide bonds by a gamma interferon-inducible lysosomal thiol reductase (GILT) is important for this process.

CD1 molecules are similar to class I molecules but bind lipids rather than peptides. Current data suggests that CD1d molecules bind lipids both in the endoplasmic reticulum and endocytic pathway. A subset of CD1d molecules physically associates and is co-transported with MHC class II molecules from the ER, through the endocytic pathway, and to the plasma membrane.

Other work centers on studies of the antiviral mechanisms of proteins inducible by Type 1 and Type 2 interferons.

CLASS II/GILT

Selected Publications
Click for PDF

Ackerman AL, Cresswell P. (2004)  Cellular mechanisms governing cross-presentation of exogenous antigens. Nat Immunol. 5(7):678-84. [Review]  

Cresswell P.  (2004)  Cutting and pasting antigenic peptides. [Perpectives: Cell biology]. Science 304: 525-527.  

Wearsch PA, Jakob CA, Vallin A, Dwek RA, Rudd PM, Cresswell P. (2004)  Major histocompatibility complex class I molecules expressed with monoglucosylated N-linked glycans bind calreticulin independently of their assembly status.  J Biol Chem.  279: 25112-25121.  

Lehner PJ and Cresswell P. (2004)   Recent developments in MHC-class-I mediated antigen presentation.  Curr Opin Immunol. 16: 82-89.  

Kang SJ, Cresswell P. (2004)  Saposins facilitate CD1d-restricted presentation of an exogenous lipid antigen to T cells. Nat Immunol. 5(2):175-81.  

Ackerman AL, Kyritsis C, Tampe R, Cresswell P. (2003)  Early phagosomes in dendritic cells form a cellular compartment sufficient for cross presentation of exogenous antigens. Proc Natl Acad Sci U S A. 100(22): 12889-94.  

Kang S-J, Cresswell P. (2002)  Regulation of intracellular trafficking of human CD1d by association with MHC class II molecules. EMBO J. 21(7): 1650-1660.  

Dick T, Bangia N, Peaper DR, Cresswell P. (2002)  Disulfide bond isomerization and the assembly of MHC class I-peptide complexes. Immunity 16: 87-98.  

Chin K-C, Cresswell P. (2001)  Viperin (cig5), an IFN-inducible antiviral protein directly induced by human cytomegalovirus. Proc Natl Acad Sci. 98(26): 15125-15130.  

Maric M, Arunachalam B, Phan UT, Dong C, Garrett WS, Cannon, KS, Alfonso C, Karlsson L, Flavell RA, Cresswell P. (2001)  Defective antigen processing in GILT-free mice. Science 294: 1361-1365.  

CCMI | Yale University School of Medicine | BBS


©2006 Yale Cell Biology
All rights reserved. Site editor - Mari Kawaguchi