Utrecht Center for Quantitative Immunology
Theoretical Biology and Bioinformatics
Faculty of Sciences
Vertebrate cells sample short peptides from endogenous
proteins, and present them to the immune system via MHC
class I molecules on the cell surface. T-cells scan the
presented peptides and need to discriminate foreign
(nonself) peptides from human (self) peptides.
We develop bioinformatics methods that can be used to identify antigenic regions in
basically any genome; these methods explained more in detail on the
We apply these methods to:
Study the evolution of antigen presentation and processing pathways.
Study co-evolution of host and its pathogen using HIV-1 as a model system
Genetic associations of infectious diseases,
Identification of neo-antigens (mutated self antigens that developed during cancer)
Improve organ transplantation when a full matched donor is not available.
MHC molecules do not only present peptides to T cells but they are also
ligands for several Natural Killer (NK) cell receptors. Because of the abundant
expression of MHC-I on many cells, NK cells remain silent to healthy tissue via
the interactions with these receptors. But when cells have a decreased
expression of MHC-I, which can occur during certain viral infections, they
become target for NK cell killing. Some of the NK receptors show a fascinating
evolutionary trade: they are polygenic and polymorphic. In the last years we
a new research line studying the evolution of the polygenecity and polymorphism
in these receptors.
Five key publications
For contact information see my home page at Utrecht University.
Tumor exome analysis reveals neoantigen-specific T-cell reactivity in an ipilimumab-responsive melanoma.
van Rooij N, van Buuren MM, Philips D, Velds A, Toebes M, Heemskerk B, van Dijk LJ, Behjati S, Hilkmann H, El Atmioui D, Nieuwland M, Stratton MR, Kerkhoven RM, Kesmir C, Haanen JB, Kvistborg P, Schumacher TN.
J Clin Oncol. 2013 Nov 10;31(32):e439-42. doi: 10.1200/JCO.2012.47.7521.
Proteome sampling by the HLA
class I antigen processing pathway. Hoof I, van Baarle D, Hildebrand WH, Kesmir C. PLoS Comput Biol. 2012;8(5):e1002517. doi:
- Degenerate T-cell recognition of peptides on
MHC molecules creates large holes in the T-cell repertoire. Calis JJ, de Boer RJ, Kesmir C. PLoS Comput Biol.
2012;8(3):e1002412. doi: 10.1371/journal.pcbi.1002412.
- A comparative analysis of viral
peptides presented by contemporary human and chimpanzee MHC class I molecules. van Deutekom HW, Hoof I, Bontrop RE, Kesmir C. J
Immunol. 2011 Dec 1;187(11):5995-6001. doi: 10.4049/jimmunol.1102236.
- A comparative study of HLA binding
affinity and ligand diversity: implications for generating immunodominant CD8+ T
Rao X, Costa AI, van Baarle D, Kesmir C. J Immunol. 2009 Feb 1;182(3):1526-32.