Using genetically fluorescent class I MHC molecules (tagged with GFP and its derivatives) we have dissected the organization of these molecules and their specialized chaperones in the endoplasmic reticulum, ER. Thus far we know that nascent class I molecules remain in the ER after peptide loading and that they interact with a number of factors some of which may carriers for export from the ER. We also have some evidence that the ER membrane is organized into domains with specialized function. Experiments are planned to study ER domain organization in detail and to resolve the nature of class I-associated molecules regulating their ER export. The same reagents and methods can be used to understand the ways in which viral proteins that suppress expression interact with class I molecules in the ER.

We also investigate the way in which antigen presentation to T cells and NK cells is affected changes in organization of class I MHC molecules at the cells surface. We are concentrating on techniques that vary the mobility of the class I molecules and on methods that change the extent to which they are clustered. It appears that cholesterol depletion of plasma membranes has large effects on antigen presentation; these effects can be mimicked by drugs that affect the membrane skeleton. In parallel we are also studying mutant class I MHC molecules with altered lateral diffusion and almost have enough data to connect the two sets of phenomena into a surprising model about the relationship between lateral diffusion and antigen presentation.

Fooksman DR, Gronvall GK, Tang Q, Edidin M. (2006) Clustering class I MHC modulates sensitivity of T cell recognition. J. Immunol. 29:11581-11588 [PubMed]

Bhatia S, Edidin M, Almo SC, Nathenson SG. (2005) Different cell surface oligomeric states of B7-1 and B7-2: implications for signaling. Proc. Natl. Acad. Sci. USA 79:5374-5385 [PubMed]

Capps GG, Pine S, Edidin M, Zuniga MC. (2004) Short class I major histocompatibility complex cytoplasmic tails differing in charge detect arbiters of lateral diffusion in the plasma membrane. Biophys. J. 185:1035 [PubMed]

Zhang X, Schwartz JC, Guo X, Bhatia S, Cao E, Lorenz M, Cammer M, Chen L, Zhang ZY, Edidin MA, Nathenson SG, Almo SC. (2004) Structural and functional analysis of the costimulatory receptor programmed death-1. Immunity 9:1209-1213 [PubMed]

Edidin M. (2003) The state of lipid rafts: from model membranes to cells. Annu. Rev. Biophys. Biomol. Struct. 3:493 [PubMed]

Rocheleau JV, Edidin M, Piston DW. (2003) Intrasequence GFP in class I MHC molecules, a rigid probe for fluorescence anisotropy measurements of the membrane environment. Biophys. J. 6:776 [PubMed]

Kwik J, Boyle S, Fooksman D, Margolis L, Sheetz MP, Edidin M. (2003) Membrane cholesterol, lateral mobility, and the phosphatidylinositol 4,5-bisphosphate-dependent organization of cell actin. Proc. Natl. Acad. Sci. USA 183:532 [PubMed]

Pentcheva, T., Spiliotis, E.T. and Edidin, M. (2002) Tapasin is retained in the endoplasmic reticulum by dynamic clustering and exclusion from endoplasmic reticulum exit sites. J. Immunol. 102:8656-8661 [PubMed]

Spiliotis, E.T., Pentcheva, T. and Edidin, M. (2002) Probing for membrane domains in the endoplasmic reticulum: retention and degradation of unassembled MHC class I molecules. Mol. Biol. Cell 293:303 [PubMed]

Pentcheva, T. and M. Edidin. (2001) Clustering of peptide-loaded MHC class I molecules for ER export imaged by fluorescence resonance energy transfer. J. Immunol. 174:7787-7791 [PubMed]

Spiliotis, E.T., H. Manley, M. Osorio, M. C. Z£¤iga, and M. Edidin. (2000) Selective Export of MHC Class I Molecules from the ER after Their Dissociation from TAP. Immunity 174:7781-7786 [PubMed]