Ian Farquhar Campbell Mckenzie
Scripps Research Institute
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Featured researches published by Ian Farquhar Campbell Mckenzie.
Journal of Molecular Biology | 2002
Vasso Apostolopoulos; Minmin Yu; Adam L. Corper; Luc Teyton; Geoffrey Allan Pietersz; Ian Farquhar Campbell Mckenzie; Ian A. Wilson
Peptides bind with high affinity to MHC class I molecules by anchoring certain side-chains (anchors) into specificity pockets in the MHC peptide-binding groove. Peptides that do not contain these canonical anchor residues normally have low affinity, resulting in impaired pMHC stability and loss of immunogenicity. Here, we report the crystal structure at 1.6 A resolution of an immunogenic, low-affinity peptide from the tumor-associated antigen MUC1, bound to H-2Kb. Stable binding is still achieved despite small, non-canonical residues in the C and F anchor pockets. This structure reveals how low-affinity peptides can be utilized in the design of novel peptide-based tumor vaccines. The molecular interactions elucidated in this non-canonical low-affinity peptide MHC complex should help uncover additional immunogenic peptides from primary protein sequences and aid in the design of alternative approaches for T-cell vaccines.
Journal of Molecular Biology | 2002
Vasso Apostolopoulos; Minmin Yu; Adam L. Corper; Wenjun Li; Ian Farquhar Campbell Mckenzie; Luc Teyton; Ian A. Wilson
The crystal structure of a non-standard peptide, YEA9, in complex with H-2Kb, at 1.5 A resolution demonstrates how YEA9 peptide can bind with surprisingly high affinity through insertion of alternative, long, non-canonical anchors into the B and E pockets. The use of alternative pockets represents a new mode of high affinity peptide binding, that should be considered when predicting peptide epitopes for MHC class I. These novel interactions encountered in this non-canonical high affinity peptide-MHC complex should help predict additional binding peptides from primary protein sequences and aid in the design of alternative approaches for peptide-based vaccines.
Archive | 2002
Geoffrey Allan Pietersz; Ian Farquhar Campbell Mckenzie
As we reflect on the use of antibodies for immunotherapy, several important points emerge. Firstly, the polyclonal antibody (PAb) response to infectious agents such as tetanus is entirely satisfactory. This polyclonal response is often present with low amounts of high-affinity IgM and IgG antibodies and is accompanied by the appropriate T- and B-cell memory so that large amounts of high affinity/avidity antibodies can be produced at short notice. On the basis of such a successful immune response, how can the immune response be used to treat cancer? Clearly the antigens are endogenous and not intrinsically immunogenic. Thus, the first problem has been to make an appropriate immune response to a nonimmunogenic antigen: a nonsequeter. However, human tumors are immunogenic in other species leading to monoclonal antibodies (MAbs) produced in the mouse. However, these antibodies are monoclonal and react with one specificity as opposed to PAbs, which react with multiple specificities; thus for MAbs there will be less antibody molecules bound to a tumor cell. In addition, for mouse MAbs the Fc piece functions poorly in humans and does not adequately mobilize various elements of an inflammatory response (by Fc and complement receptors). Thus for the most part, mouse antibodies alone have not proven useful for either the detection or treatment of solid tumors. It is clear that the antibodies had to made more potent and Paul Ehrlich’s suggestion of converting them to “magic bullets” was reintroduced when MAbs began to appear in the 1980s for the treatment of cancer.
Archive | 1994
Ian Farquhar Campbell Mckenzie; Vasso Apostolopoulos; Geoff Allan Pietersz
Archive | 1997
Ian Farquhar Campbell Mckenzie; Vasso Apostolopoulos; Geoff Allan Pietersz
Archive | 1999
P. Mark Hogarth; Maree S. Powell; Ian Farquhar Campbell Mckenzie; Kelly F. Maxwell; Thomas P. J. Garrett; Vidana Epa
Archive | 1999
Jonathan B. Baell; Thomas P. J. Garrett; P. Mark Hogarth; Barry Ross Matthews; Tom McCarthy; Geoffrey Allan Pietersz; Maree S. Powell; Ian Farquhar Campbell Mckenzie; Kelly F. Maxwell; Vidana Epa
Archive | 2001
Ian Farquhar Campbell Mckenzie; Geoff Allan Pietersz; Vasso Apostolopoulous
Archive | 1994
Ian Farquhar Campbell Mckenzie; Vasso Apostolopoulos; Geoff Allan Pietersz
Archive | 1986
Ian Farquhar Campbell Mckenzie; Geoffrey Allan Pietersz; Jerry Kanellos