The relationship between immunodominance, DM editing, and the kinetic stability of MHC class II:peptide complexes
Article first published online: 23 SEP 2005
Volume 207, Issue 1, pages 261–278, October 2005
How to Cite
Sant, A. J., Chaves, F. A., Jenks, S. A., Richards, K. A., Menges, P., Weaver, J. M. and Lazarski, C. A. (2005), The relationship between immunodominance, DM editing, and the kinetic stability of MHC class II:peptide complexes. Immunological Reviews, 207: 261–278. doi: 10.1111/j.0105-2896.2005.00307.x
- Issue published online: 23 SEP 2005
- Article first published online: 23 SEP 2005
Summary: Immunodominance refers to the restricted antigen specificity of T cells detected in the immune response after immunization with complex antigens. Despite the presence of many potential peptide epitopes within these immunogens, the elicited T-cell response apparently focuses on a very limited number of peptides. Over the last two decades, a number of distinct explanations have been put forth to explain this very restricted specificity of T cells, many of which suggest that endosomal antigen processing restricts the array of peptides available to recruit CD4 T cells. In this review, we present evidence from our laboratory that suggest that immunodominance in CD4 T-cell responses is primarily due to an intrinsic property of the peptide:class II complexes. The intrinsic kinetic stability of peptide:class II complexes controls DM editing within the antigen-presenting cells and thus the initial epitope density on priming dendritic cells. Additionally, we hypothesize that peptides that possess high kinetic stability interactions with class II molecules display persistence at the cell surface over time and will more efficiently promote T-cell signaling and differentiation than competing, lower-stability peptides contained within the antigen. We discuss this model in the context of the existing data in the field of immunodominance.